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Arnold Joseph O. Geronimo, Mari Erika Joi F. Bancual, Karl Anthony L. Ko, Lycon Marie L. Soliba, Jeric John C. Ildefonso, Angelica Mae B. Soriano, Alta Christine Marie M. Tagalog, Nikolai E. Acosta, Vincent S. Ang, Mariebon A. Apigo, et al.
Indonesian Journal of Cancer Chemoprevention, Volume 11; doi:10.14499/indonesianjcanchemoprev11iss3pp124-133

Abstract:
Cancer is one of the significant causes of mortality worldwide. Studies on antineoplastic drugs focused on natural products have revealed several mechanisms to inhibit cancer cells. Bugnay (Antidesma bunius) leaves showed potentials due to its activity observed against brine shrimp and breast cancer cells. However, there is still limited knowledge about its activity against other human cancer cells. This study focused on determining the phytochemical compounds in A. bunius leaves extract, the free radical scavenging activity of the extract using the Diphenylpicrylhydrazyl (DPPH) method, and in vitro cytotoxic activity against two cancer cell lines, namely HCT-116 human colorectal and A549 human lung adenocarcinoma cancer cell lines by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The phytochemicals identified were unsaturated lactones, flavonoids, phenolics, diterpenes, saponins, tannins, carbohydrates, and reducing sugars. The extract showed significant free radical scavenging activity and a direct correlation of activity with concentration levels. It also exhibited cytotoxic activity against HCT-116 human colorectal and A549 human lung adenocarcinoma. Hence, A. bunius leaves have the potential to be a source of antioxidant and antineoplastic compounds. This warrant further isolation of the compounds for chemotherapeutic purposes.Keywords: Antidesma bunius, Bugnay, Cancer, Cytotoxicity, Radical
Puguh Indrasetiawan, Sari Haryanti, Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention, Volume 11; doi:10.14499/indonesianjcanchemoprev11iss3pp168-186

Abstract:
Breast cancer remains as one of the highest causes of cancer-related deaths in the world, including Indonesia. In spite of following the standard protocol therapy, some patients in developing countries consume medicinal herbs as an alternative, complementary, as well as supportive therapies. Several herbs have been recognized to be used for this purpose. Annona muricata, Curcuma longa, Curcuma zanthorrhiza, Curcuma zedoaria, Phyllanthus urinaria, Gynura procumbens, Garcinia mangostana, Morinda citrifolia, and Nigella sativa are some of the plants used as chemopreventive agents with several formulas. Various types of extracts of Annona muricata show anticancer activities in vitro and in vivo. Curcumin, obtained from Curcuma longa and Curcuma zanthorrhiza, acts as p53 regulator and pro-oxidant in MCF-7 cells and also acts as a fatty acid synthase inhibitor in MDA-MB-231 cells. Xanthorrhizol from Curcuma zanthorrhiza has pro-apoptotic activity via modulation of Bcl-2, p53, and PARP-1 protein levels. Curcuma zedoaria contains curcumenone, curcumenol and curdion, which show pro-apoptotic activity in various cell lines and a cancer-induced mouse model. Corilagin and geraniin from Phyllanthus urinaria have different pro-apoptotic effects, in which, the corilagin-caused apoptotic effect is mediated by extrinsic and mitochondrial pathways, whereas geraniin induces apoptosis via ROS-mediated stimulation, both in MCF-7 cells. Thymoquinone from Nigella sativa has been extensively studied for its anticancer activities in recent years. Plants are cultivated, collected and mixed depending on the use as herbal medicines. Active compounds might be formulated if deemed possible. The development of more potential derivatives is also necessary to produce more optimum anti-cancer agents. In conclusion, Indonesian plants and their active constituents show potential activities to be developed as chemopreventive agents.Keywords: Indonesian medicinal herbs, breast cancer, active constituents, molecular targets
Marsya Yonna Nurrachma, Gergorius Gena Maran, Nindya Budiana Putri, Yuni Fajar Esti, Adam Hermawan, Edy Meiyanto, Riris Istighfari Jenie
Indonesian Journal of Cancer Chemoprevention, Volume 11; doi:10.14499/indonesianjcanchemoprev11iss3pp103-114

Abstract:
Fingerroot (Boesenbergia pandurata) is an Indonesian herb, with anti-proliferation and anti-migratory effects against several cancer cells. This study aims to investigate the anticancer property of Fingerroot Extract (FE) in combination with doxorubicin (Dox) against 4T1, a metastatic breast cancer cell lines. FE was prepared by 96% ethanol maceration and characterized by thin-layer chromatography analysis. FE was subjected to a cytotoxicity test with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay alone or in combination with 10 nM Dox against 4T1 cells. Cytotoxic effect was then confirmed by measure reactive oxygen species (ROS) intracellular level using 2’,7’-dichloroflourescin diacetate (DCFDA)-staining flow cytometry-based assay. The anti-migratory effect was observed using scratch wound healing assay and gelatin zymography to investigate matrix metalloproteinase (MMP)-9 expression. FE showed a cytotoxic effect with an inhibitory concentration 50 (IC50) value of 25.5±3.9 μg/mL and performed an improved effect in combination with 10 nM Dox. A single treatment of FE decreased ROS intracellular level, while in combination with Dox, FE increased the ROS intracellular level. Further, at 42 h observation, FE and its combination with Dox inhibited the migration of 4T1 cells with % closure of 82.6 and 82.5, respectively, correlates with a significant decrease of MMP-9 expression. Overall, FE performs a cytotoxic activity and anti-migration activity on 4T1 breast cancer cells.Keywords: Boesenbergia pandurata, cytotoxic, ROS, anti-migration, 4T1
Muhammad Hasan Bashari , Eveline Yuniarti, Tenny Putri, Nurul Qomarilla, Dikdik Kurnia, Mieke Hermiawati Satari, Edhyana Kusumastuti Sahiratmadja, Fathul Huda
Indonesian Journal of Cancer Chemoprevention, Volume 11; doi:10.14499/indonesianjcanchemoprev11iss3pp115-123

Abstract:
Breast cancer (BC) and cervical cancer (CC) have a high prevalence and mortality rate worldwide. Despite the availability of advanced treatment, resistance to conventional chemotherapies has emerged. Myrmecodia pendens, one of the species of Sarang Semut (local name), possess a potential of antitumor effects by inducing cell death different cancer cell entities. This study aimed to assess anti-tumor activities of n-hexane fraction of M. pendens in inhibiting cell survival and cell migration in BC and CC cells. M. pendens was extracted in methanol then fractionated using n-hexane or ethyl acetate. BC cells including MCF-7 (luminal A), HCC-1954 (HER2+) cells and CC Hela cells were treated with M. pendens extracts to evaluate cytotoxic activity using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay as well as anti-cell migration using scratch assay. We also analyzed inhibitory concentration 50 (IC50) of n-hexane fraction in BC and CC cells. We started with comparing cytotoxicity activities of methanol extract, ethyl acetate and n-hexane fractions of M. pendens. Data showed that the n-hexane fraction was the most potent inducing BC cell death. Therefore, we used the n-hexane fraction for further experiments. Interestingly, IC50 of this fraction in HCC-1954 and Hela cells were lower than in MCF-7 cells, 16; 13 and 60 ppm, respectively. Moreover, the low concentrations of n-hexane fraction inhibited HeLa cells migration, compared to control group (p
Roihatul Mutiah, Yen Yen Indrawijaya, Dwi Puspita
Indonesian Journal of Cancer Chemoprevention, Volume 11; doi:10.14499/indonesianjcanchemoprev11iss3pp144-153

Abstract:
Chrysanthemum cinerariifolium (Trev.) is a plant that has potential as an anticancer. This study aimed to predict the inhibitor of estrogen alpha and toxicity of compounds in 96% ethanol extract of C. cinerariifolium leaves in silico. Prediction of the activity of metabolic profiling compounds produced by UPLC QToF MS/MS ethanol extract 96% of C. cinerariifolium leaves towards alpha estrogen receptors (ER-α) (5W9C) was carried out using Molegro Virtual Docker. The docking results showed that the compound (2-Methyl-1,4-piperazinediyl) bis-[(3,4,5-trimethoxyphenyl)-methanone and Azoxystrobin have good activity compared to Tamoxifen, because these compounds have a lower Rerank Score. The activity of the test compound is also shown by the bonding of active amino acids (Arg 394, Asp351, Glu 353, and Val 533). As for the toxicity class based on Globally Harmonized System (GHS) and Lethal Dose 50 (LD50) values, the ten docking compounds had a relatively low toxicity.Keywords: C. cinerariifolium, breast cancer, alpha estrogen, cytotoxic activity, toxicity
Rohmad Yudi Utomo, Muthi' Ikawati, Dyaningtyas Dewi Pamungkas Putri, Irfani Aura Salsabila, Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention, Volume 11; doi:10.14499/indonesianjcanchemoprev11iss3pp154-167

Abstract:
The COVID-19 becomes worse with the existence of comorbid diseases such as cardiovascular diseases, metabolic syndromes, inflammation, degenerative diseases, as well as cancer. Therefore, a comprehension approach is needed to combat such comorbid conditions, not only focusing on the virus infection and replication but also directed to prevent the raising comorbid symptoms. This study analyzed the potential natural compounds, especially diosmin and hesperidin, as an anti-SARS-CoV-2 and chemopreventive agent against several COVID-19 comorbid diseases by using an in-silico method. Diosmin and hesperidin together with other natural compounds and existing viral drugs (lopinavir, nafamostat, and comastat) were docked into several proteins involved in SARS-CoV-2 infection and replication namely SARS-CoV-2 protease (PDB:6LU7), spike glycoprotein-RBD (PDB:6LXT), TMPRSS2, and PD-ACE2 (PDB:6VW1) using MOE software. The interaction properties were determined under docking score values. The result exhibited that diosmin and hesperidin performed superior interaction with all the four proteins compared to the other compounds, including the existing drugs. Moreover, under literature study, diosmin and hesperidin also elicit good chemopreventive properties against cardiovascular disorder, lung and kidney degeneration, as well as cancer development. In conclusion, diosmin and hesperidin possess high opportunity to be used for the COVID-19 and its the comorbid diseases as chemopreventive agents.Keywords: chemoprevention, COVID-19, diosmin, hesperidin, SARS-CoV-2 infection
Hadi Sunarto, Setyo Trisnadi, Agung Putra, Nur Anna Chalimah Sa'dyah, Arya Tjipta, Chodidjah Chodidjah
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 134-143; doi:10.14499/indonesianjcanchemoprev11iss3pp134-143

Abstract:
Full-thickness wound are areas damage of skin associated with loss of epidermis and dermis. The wound healing mechanism consists proliferation, migration and remodeling. Hypoxic conditional medium of mesenchymal stem cells (HMSCs-CM) contains lots of soluble molecules, such as protein growth factor and cytokine anti-inflammation. The soluble molecule of HMSCs-CM plays a critical role in wound healing by upregulation of VEGF and collagen synthesis. The objective of this study was to evaluate the effect of HMSCs-CM on VEGF and collagen concentrations in rats with incised wounds. The methods of this study were an experimental animal study with post-test only control group design was performed involving 24 Wistar rats. The rats were randomized into four groups consisting of sham, control and two treatment groups (gel of HMSCs-CM at doses of 200 μL and 400 μL). The VEGF levels and collagen density were analyses using ELISA assay and Masson-trichome specific staining, respectively. One-way ANOVA and Post Hoc LSD were used to analyses the data. The results of this study showed that a VEGF levels was significant increased on day 6 with doses-dependent manner. Interestingly, the VEGF levels gradual decrease on day 9. In addition, the decreased of VEGF levels on day 9 in this study in line with our findings in which we found there was a trend in the decreased of collagen density, it indicated the completion of remodeling phase and there has been an acceleration in wound healing. This study demonstrated that HMSCs-CM were able to regulate VEGF levels and collagen synthesis in accelerate wound healing. The role of HMSCs-CM stimulate cutaneous wound healing should be clarified further.Keywords: hypoxic conditional medium of mesenchymal stem cells (HMSCs-CM), vascular endothelial growth factor, collagen synthesis, paracrine factors
Ammar A. Razzak Mahmood Kubba, Wurood Ahmed Shihab, Nada Naji Al-Shawi, Majid Shamki Jabir
Indonesian Journal of Pharmacy, Volume 31; doi:10.14499/indonesianjpharm31iss2pp92

Abstract:
A new series of 4-(6-(4-substituted phenyl)-7H[1,2,4] triazolo[3,4b][1,3,4]thiadiazin-3-yl) phenol was synthesized and explored for anti-tubulin activity using in silico and in vitro assay models. The starting nucleus, ethyl-4-hydroxybenzoate was treated with hydrazine hydrated, and converted to 4-hydroxybenzohydrazide (1). Then, (1) was stirred with CS2 and KOH in dry EtOH to afford 2-(4-. hydroxyl benzoyl)hydrazine-1-carbodithioate, as a potassium salt (2). Compound (2) was used directly and refluxed with hydrazine hydrate to yield a parent nucleus, 4-(4-amino-5-mercapto-4H-1,2,4-triazol-3-yl)phenol (3). The target compounds (4-7), were synthesized by refluxing compound (3) with various substituted phenacyl bromides using sodium acetate as a abase, The new compounds (3-7) were characterized using different spectroscopic analysis techniques including IR, and 1HNMR. The anticipated modes of binding to α- tubulin were also investigated by means of a molecular docking experiment. The binding mode revealed good agreement with the in vitro work with binding energies of (-38.77 and -37.50 kcal/ mol) for the most potent compounds 7 and 4, respectively. The effect of synthetic novel compounds on cancer cell lines proliferation was screened by MTT assay. The ability of the synthetic compounds to induce apoptosis process was tested using acridine orange/ ethidium bromide staining. The synthetic novel compounds exhibited potent inhibitory effects on the growth and viability of cancer cell lines SKOV-3 and AMJ-13 cells. They inhibited the proliferation and growth of cancer cell lines at low concentrations, with IC50 values ranging from10.44 to 19.67 µg/mL against SKOV-3 cells, and for AMJ-13 cells, the IC50 values were11.35 to 20.52 µg/mL. The effect of the synthetic compounds on the cell growth, and proliferation of cancer cell lines was associated with increased apoptosis.Our results demonstrated that the target compounds inhibited cancer cell lines proliferation, with a mechanism of action parallel to that of other tubulin inhibitors
Ngoc-Van Thi Nguyen
Indonesian Journal of Pharmacy, Volume 31; doi:10.14499/indonesianjpharm31iss2pp69

Abstract:
Concerns are growing about human exposure to endocrine-disrupting chemicals (EDCs), especially during the preadolescent development stage. Parabens are prevalent EDCs widely used as additives in cosmetics. So, the determination of parabens in such products is important. In this study, we developed a reliable and sensitive method to determine simultaneously nine common parabens (methylparaben, ethylparaben, phenylparaben, benzylparaben, penthylparaben, and two groups of isomeric compounds include propylparaben, isopropyl paraben, and butylparaben, isobutylparaben) in cosmetics products. The QuEChERS and solid-phase extraction techniques are used for extraction parabens from non-surfactant cosmetics (perfume, mouth wash solution) and surfactant cosmetics (shampoo, cream, gel), respectively and quantified by using ultra-performance liquid chromatography coupled with the ultraviolet-visible detector. All nine compounds showed good linearity with regression coefficients predominantly above 0.990. The LOD and LOQ of parabens were 0.07 µg/mL; 0.2 µg/mL, respectively. The recoveries ranged from 80 to 110% with the relative standard deviations below 8%. The developed method was successfully applied to determine parabens in various commercial cosmetic products from a local supermarket and the total parabens concentrations are in a wide-ranged from 2.0 to 1270 mg/kg.
Devyanto Hadi Triutomo, Ika Puspitasari, Ratna Asmah Susidarti
Indonesian Journal of Pharmacy, Volume 31; doi:10.14499/indonesianjpharm31iss2pp116

Abstract:
The use of deltamethrin and cypermethrin insecticides to control pests has been implemented in Indonesia. Irregular and excessive use of insecticides can have toxic effects on the male reproduction system. Deltamethrin and cypermethrin insecticides can inhibit androgen biosynthesis and disrupt the growth of sperm. Therefore, this research is conducted to find out the effect of deltamethrin and cypermethrin insecticides toward the level of intratesticular testosterone in male Wistar strain rats. This research is conducted in vivo using male Wistar strain rats. Nine rats are divided into three groups of treatment, namely control group, deltamethrin group with 0.26 mg/kg of weight, and cypermethrin group with 0.26 mg/kg of weight. Treatment is conducted every day for 15 days orally, and then the rats are dissected to take their testicles. Testicles are chopped and their intratesticular homogenates are taken by adding the medium of DMEM and collagenase (0.25 mg/mL). The measurement of the level of testosterone is conducted by using Electrochemiluminescence immunoassay (ECLIA) method. Data on the change of the increase of body weight, organ weight, and the level of testosterone is analyzed statistically using the one-way ANOVA test. The research result shows that giving 0.26 mg/kg of weight of deltamethrin and 0.26 mg/kg of weight of cypermethrin does not affect the increase in body weight, relative weight of the reproductive organ, and the level of intratesticular testosterone of male Wistar strain rats.
Sara E. Gomaa, Matthew Friedersdorf, Hesham Ali El Enshasy, Mb Abou-Donia
Indonesian Journal of Pharmacy, Volume 31; doi:10.14499/indonesianjpharm31iss2pp108

Abstract:
In this research, the biological activities of five plant extracts from family Apiaceae; Italian Parsley (Petroselinum neapolitanum), Fennel (Foeniculum vulgare), Celery (Apium graveolens), Cilantro (Coriandrum sativum) and Dill (Anethum graveolens), were studied. Antiproliferative effect of eleven ethanol crude extracts was tested in Human Cervical (Hela) cancer cells. Results clearly demonstrated that all plant extracts showed high significant difference when compared to the negative control (DMSO).Parsley leaves extract, cilantro leaves extract and cilantro stems extract showed no significant difference with the positive control (Actinomycin D). As for, fennel bulb extracts, fennel stalks extracts, celery stems gave better results than the positive control with no significant difference through the 24, 48 and 72 h treatment. There were no significant difference between Fennel extracts and the positive control, which showed high effect on the cancer cells survival. There were no significant difference between both extracts of Cilantro leaves and stems through each time but the best result was after 72 h of treatments. Regarding Dill leaves and stems, cell numbers recorded no significant difference between the both on time dependent manner. Further investigation for ethanolic extracts of parsley leaves, fennel bulb, fennel stalks, celery stems, cilantro leaves and cilantro stems which showed better results than using the commercial drug Actinomycin D (25ml/ml) for 24 h treatment or less depending on concentrations manner. Also, further investigation on different types of cancer cell lines to avoid the toxic effect of chemotherapy.
Dmitry Igorevich Pozdnyakov, Similla Adzhiahmetova, Nadezhda Chervonnaya, Andrey Mamleev, Eduard Oganesyan
Indonesian Journal of Pharmacy, Volume 31; doi:10.14499/indonesianjpharm31iss2pp131

Abstract:
To date, stress is a common medical and socially significant disease that requires rational pharmacotherapeutic correction.The anti-stress properties of ethnolic and aqueous extracts obtained from leaves of Ribes nigrum L., inflorescences of Gaillardia pulchella Foug., stems of Lysimachia punctata L were studied in this work. Acute stress was modeled by immobilization of rats for 2 hours. The test-extracts were administered per os prophylactically in a dose of 1/20 of LD50 (2000 mg/kg). The following parameters were evaluated: organs mass coefficient (adrenal glands, thymus, spleen), the number of stomach erosion; the biochemical changes in the blood serum (adrenaline, cortisol, total protein and glucose concentration); the mitochondrial function parameters in brain and myocardium (evaluation of mitochondrial pore transitional permeability opening and mitochondrial membrane potential). 70% ethanol extract from Gaillardia pulchella Foug. inflorescences has the highest anti-stress activity, the course application of which contributed to the normalization of the weight index of organs, a decrease in glucose concentration by 64.5% (p
Yoni Astuti, Aulia Primasari
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 60-66; doi:10.14499/indonesianjcanchemoprev11iss2pp60-66

Abstract:
Colorectal cancer is third rank on the cancer cases in Indonesia. To cure the cancer needs big cost and lot of effort. On the other side, the side effect of medicine or chemotherapy on patient need to reduce. Cancer cell spread to other tissue based on its migration and invasion ability. Citrus reticulata peel contains flavonoid such as Tangeretin and Nobiletin, both of this compounds have anticancer activity. The aims of this study is to reveals the potency of ethanol extract of Citrus reticulata peel on the inhibition of migration on WiDr colon cancer cells. The toxicity of ethanol extract of Citurs reticulata peel on WiDr colon cancer line was measured using 3-(4,5-dimethyltiazol-2-il)-2,5-diphenyltrazolium bromide (MTT) assay and investigate the cell migration was using scratch wound healing assay. The ethanol extract of Citrus reticulata peel showed the value of inhibitory concentration 50 (IC50) was 184.5 μg/mL, this result categorize as moderate cytotoxic. Meanwhile the migration assay showed that the deceleration of migration occurred on 0.5 IC50, 0.33 IC50 and 0.25 IC50 during 24 h and 36 h incubation, event thought there were not significant different (p>0.05). The ethanol extract of Citrus reticulata peel has a potential migration inhibition on WiDr cell line.Keywords: Citrus reticulata, WiDr cell line, migration
Poppy Anjelisa Zaitun Hasibuan, Rosa Gloria Sitanggang, Robbani Syahfitri Angkat
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 75-83; doi:10.14499/indonesianjcanchemoprev11iss2pp75-83

Abstract:
Menopause is a hypoestrogenic condition due to decreased function of the ovary. During menopause there is no reserved ovum in the ovary, as a result the synthesis of estrogen by the follicles does not take place. Deficiency of estrogen can lead to discomfort and decrease in the women quality of life. Therefore, supplements from natural resources to reduce menopausal symptoms will be needed. The objectives of the study were to determine the effect of mahogany seeds ethanolic extract (MSEE) on the development of uterus, bone density, and mammae gland proliferation on ovariectomized rats. Extract was made by maceration using 96% ethanol as the solvent, then the study of estrogenic effect was carried out on 30 female rats which were divided into 6 groups. Group 1 (normal control), group 2 (positive control) given estradiol dose of 0.18 mg/kg body weight (BW), group 3 (negative control) given Na-CMC 1% and group 4, 5, 6 given MSEE orally for 14 consecutive days with doses of 50, 100, 200 mg/kg BW. Data were analysed using ANOVA then continued with Tukey HSD Post Hoc test to see the differences between the treatments. The results of the study showed that MSEE was able to increase the weight of the uterus, the length of estrus phase in the estrus cycle, bone density and the mammae gland proliferation of rats. The results concluded that MSEE has phytoestrogenic effect on ovariectomized rats.Keywords: phytoestrogen, ovariectomy, uterus weight, bone density, mammae proliferation
Puspaneka Wijayanti, Sri Pramestri Lastianny, Suryono Suryono
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 54-59; doi:10.14499/indonesianjcanchemoprev11iss2pp54-59

Abstract:
Carbonated hydroxyapatite is frequently used as bone graft material in dentistry. It is highly biocompatible, has osteoconductive properties, and functions as a drug delivery system. Propolis is a natural product from bees that has antibacterial and anti-inflammatory effects and is capable of accelerating wound healing. Incorporating propolis into carbonated hydroxyapatite was expected to enhance the wound-healing process by stimulating fibroblast growth and regenerating alveolar bone in the treatment of periodontitis. The aim of this study was to evaluate the effect of carbonated hydroxyapatite with incorporated propolis on the viability of NIH 3T3 fibroblast cells. This study used three treatment groups [carbonated hydroxyapatite with various concentrations of incorporated propolis (5%, 7.5%, and 10%)] and one control group (carbonated hydroxyapatite with no propolis). An MTT assay was carried out to assess cell viability, and absorbance readings were performed by using an ELISA reader. The data were analyzed by using one-way ANOVA. The results showed significant differences between all groups, and carbonated hydroxyapatite with 10% incorporated propolis has the highest cell viability level of all groups, while the control group has the lowest cell viability. In conclusion, adding propolis to carbonated hydroxyapatite could increase the growth of NIH 3T3 fibroblast cells. Keywords: Carbonated hydroxyapatite, Propolis, NIH 3T3 fibroblast cells, MTT assay
Muhammad Hasan Bashari , Fachreza Aryo Damara, Isna Nisrina Hardani, Gita Widya Pradini, Tenny Putri, Eko Fuji Ariyanto
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 90-96; doi:10.14499/indonesianjcanchemoprev11iss2pp90-96

Abstract:
Cervical cancer is one of the most leading causes of women death. Currently, paclitaxel is still one of the main therapeutic regimens for cervical cancer patients. However, some patients developed to be paclitaxel-resistant. Hence, studies to find out the novel strategies to resolve this problem are important. Generating resistant cancer cell lines can be utilized as the potent tool to evaluate the efficacy of any therapeutic agent toward cancer drug-resistant problems. Current studies describing the methods to establish chemoresistance are lacking. Moreover, study in Indonesia conducting chemoresistance in cell line is limited. This study was aimed to elaborate the characteristics of HeLa cells during generation of paclitaxel-resistant cervical cancer cells. The parental HeLa cells were exposed to an escalating concentration of paclitaxel for a long time period. Subsequently, cells were divided into two groups for the evaluation of resistance characteristics. The values of inhibitory concentration 50 (IC50) and inhibitory concentration 90 (IC90) were analyzed using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Our data showed that the longer exposing periods of paclitaxel, the higher IC50 and IC90 values of HeLa cells are. IC90 of paclitaxel in HeLa Pac RB was increased from 69 pM, 440 pM, 2,561 pM and 10,337 pM on 0th, 1st, 2nd, 3rd and 4th months, respectively. Interestingly, the resistant cells were recovered to be paclitaxel-sensitive when they were not being continuously exposed to paclitaxel. In addition, the paclitaxel resistant cells become less sensitive against 5-FU but not doxorubicin, cisplatin and etoposide. We were able to generate cervical cancer HeLa paclitaxel-resistant cell line. These cell line could potentially be utilized for further studies in order to understand the molecular mechanisms of drug resistance in cervical cancer and as a tool for cancer drug discovery.Keywords: cervical cancer, drug resistant cell line, paclitaxel resistant cells, stepwise escalating concentration.
Banun Kusumawardani, Qonita Nafilah Febi, Malihatul Rosidah, Deri Abdul Azis, Endah Puspitasari, Ari Satia Nugraha
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 97-102; doi:10.14499/indonesianjcanchemoprev11iss2pp97-10

Abstract:
Flavonoid has potential bioactivity as anticancer agents. The flavonoid of cultivated tobacco (Nicotiana tabacum), locally known as “Kasturi”, leaves was screened for its cytotoxicity against MCF-7 human breast cancer cells and non-transformed Vero cells (African normal cell kidney line) in different concentrations. This study aimed to examine the cytotoxic potential of the flavonoid of Kasturi tobacco leaves against MCF-7 human breast cancer cells. Flavonoid obtained from methanolic extracts of Kasturi tobacco leaves, which have been purified from nicotine. The flavonoid of Kasturi tobacco leaves with concentrations of 20 to 640 μg/mL were exposed to MCF-7 and Vero cells for 24 h. Cell viability was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Flavonoid of Kasturi tobacco leaves with concentrations of 160 μg/mL decreased the MCF-7 cell viability more than 50%, with an inhibitory concentration 50 (IC50) value of 148.41 μg/mL. Meanwhile, it inhibited 50% of Vero cell viability at 255.35 μg/mL. The flavonoid of Kasturi tobacco leaves has cytotoxic activity on MCF-7 cells, and might be a potential alternative agent for human breast cancer therapy.Keywords: flavonoid, tobacco leaves, human breast cancer cells, anticancer activity
Roihatul Mutiah, Farenza Okta Kirana, Rahmi Annisa, Ana Rahmawati, Ferry Sandra
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 84-89; doi:10.14499/indonesianjcanchemoprev11iss2pp84-89

Abstract:
Yellow root (Arcangelisia flava (L.) Merr.) has been scientifically known to have potential as an antimalarial, antibacterial, antioxidant, and anticancer. The purpose of this study was to determine the profile of alkaloid content and cytotoxicity of yellow root extract from several regions in Kalimantan. The alkaloid content was tested using the thin layer chromatography (TLC) method with dragendorf reagent. Cytotoxic in vitro test was conducted against WiDr colorectal cancer cells using the 3-(4,5-dimethylthiazol-2-il)-2,5-diphenyltetrazolium bromide (MTT) assay. Yellow roots were collected from Samarinda city, Banjarmasin city, Barito Timur regency, Malinau district, and Balikpapan City. The MTT inhibitory concentration 50 (IC50) of yellow root extracts were 573.308 μg/mL; 582.857 μg/mL; 296.326 μg/mL; 114.119 μg/mL; and 320.162 μg/mL respectively. Results of the compound identification indicated that alkaloid was found in A. flava from all regions. Alkaloids of A. flava extract should be investigated further in order to find possible active agent that could decrease the viability of WiDr colorectal cancer cells.Keywords: Arcangelisia flava, Borneo, colorectal cancer, Kalimantan, WiDr cells.
Nunung Ainur Rahmah, Harliansyah Harliansyah, Fransiscus D. Suyatna, Mpu Kanoko, Primariadewi Rustamadji, Joedo Prihartono, Samuel Johny Haryono, Bethy Suryawati Hernowo
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 67-74; doi:10.14499/indonesianjcanchemoprev11iss2pp67-74

Abstract:
Curcumin has been reported with an in vitro the cytotoxic effect on several human cancer cells. However, reports on the mode of action and detail mechanism of curcumin in breast cancer disease are limited. Hence, curcumin’s effect on the human breast cancer cell line MCF-7 and MDA-MB-468 was investigated. The MCF-7 and MDA-MB-468 breast cancer cells line were given curcumin in several doses. The anti-proliferation activity of curcumin was determined using the MTS cell viability test and caspase-3 activity was used to detect apoptosis using flowcytometry. The expression of Ras-association domain family 1 isoform A (RASSF1A) and Bax protein in cells was evaluated by ELISA analysis. Kruskal-Wallis followed by the Mann-Whitney test and the Spearman correlation tests were used to asses correlation among RASSF1A, Bax, and caspase-3. Cytotoxicity of curcumin on MCF-7 was lower than that of MDA-MB-468 (75.73 μg/mL and 380.79 μg/mL). The concentration of curcumin at 80 μg/mL induced apoptosis mainly through the intrinsic pathway by caspase-3 activation. Curcumin also showed an anti-proliferative activity as shown by the increase of RASSF1A and Bax protein. Curcumin mediates anti-proliferative and apoptotic effect through the activation of RASSF1A and Bax. Our research data adds information about the role of curcumin in epigenetic events through RASSF1A protein.Keywords: Bax, caspase-3, curcumin, MCF-7, MDA-MB-468, RASSF1A
Rozana Oktaviary, Ilma Nugrahani, Slamet Ibrahim Surantaatmadja, Tutus Gusdinar Kartawinata, Cintya Nurul Apsari
Indonesian Journal of Pharmacy, Volume 31; doi:10.14499/indonesianjpharm31iss2pp78

Abstract:
Quantitative analysis of bioactive peptide mostly conducted by measuring the activity. While the determination of peptide content in natural sources has been conducted using various instruments, vibrational spectroscopy remains underutilized. Here, we attempted new developed method in peptide quantification and degradation kinetic analysis using Fourier-Transform Infrared Spectroscopy. Bovine Serum Albumin was used as standard protein in method development and validation. Peptide content was estimated by converting peak area to concentration. The method was used to estimate peptide content in Canarium nut protein and its hydrolysates, which potentially hold biological activity. Kinetic study was conducted with microwave as an accelerator for hydrolysis, an apparatus rarely used in peptide study. Amide I band on wavenumber range of 1724.05-1619.91 cm-1 was selected for analysis, considering its selectivity and linearity. The method also met other validation requirement, including accuracy and precision. When applied in quantitative analysis, the method was able to calculate peptide content decrease in Canarium nut protein after hydrolysis using papain (38.24%), pepsin (33.67%) and alkaline reagent (28.53%). In kinetic study, microwave-assisted peptide degradation exhibited logarithmic profile with the equation of y=-0.148ln(x)+0.9591 and R² value of 0.963. Based on these results, FTIR is useful in estimating peptide content and in analyzing degradation kinetic profile.
Oktavia Indrati, Ronny Martien, Abdul Rohman, Akhmad Kharis Nugroho
Indonesian Journal of Pharmacy, Volume 31; doi:10.14499/indonesianjpharm31iss2pp124

Abstract:
Background: Optimization of self-nanoemulsifying drug delivery system (SNEDDS) formulation is an important step to obtain optimal formulation with desired characteristics.Objective: This present study was aimed to utilize simplex lattice design in optimizing andrographolide SNEDDS.Method: Simplex lattice design was employed to optimize andrographolide SNEDDS in which component of SNEDDS was selected as the independent factor while the charactheristics of SNEDDS was used as the responses. Capryol-90, Kolliphor RH 40, and propylene glycol were selected as the oil, surfactant, and co-surfactant, respectively. Optimization of andrographolide SNEDDS formulation was based on their characteristics including emulsification time, droplet size, and drug content. The optimized SNEDDS formulation was evaluated for emulsification time, droplet size, drug content, and zeta potensial.Results: The emulsification time, droplet size, drug content, and zeta potensial of the optimized andrographolide SNEDDS was found to be 1.21±0.03 min, 44.02±0.67 nm, 6.69±0.08 mg/g, and -40.63±0.76 mV, respectively.Conclusion: This result suggested that simplex lattice design is a suitable for efficiently optimizing the formulation of andrographolide SNEDDS.
Riris Jenie, Sri Handayani, Ratna Asmah Susidarti, Edy Meiyanto
Indonesian Journal of Pharmacy, Volume 31; doi:10.14499/indonesianjpharm31iss2pp84

Abstract:
Ethanolic extract and brazilein-containing fraction of Caesalpinia sappan L., has been reported to inhibit cell proliferation in T47D (ER+ PR+/- cell, Luminal A subtype model). The Luminal A subtype is the most common subtype of breast cancer in Indonesian women. In this study, we explored the activity of the reduced form of brazilein, i.e. brazilin, in T47D cells proliferation and the mechanism that involved. The cytotoxicity activity of brazilin was observed using MTT assay. While the cell cycle modulation analysis was done by using flowcytometry, and the senescence assay was observed using S-A-β-galactosidase assay. The results showed that brazilin inhibited cell growth in a dose-dependent manner with an IC50 value of 50μM (or 14.3μg/mL). That was higher than a brazilein-containing fraction, which was reported previously by our group to have an IC50 value of 68μg/mL against the same cell. Cell cycle analysis showed that cells treated with brazilin were accumulated at the G2/M phase in a dose-dependent manner. Furthermore, cells treated with a combination of brazilin and doxorubicin was accumulated at the G2/M phase and sub G1 phase. Cells accumulation at sub G1 phase indicates that the cells undergo apoptosis. Our data of S-A-β-galactosidase assay showed that cells treated with 1/4IC50, 1/2IC50, and IC50 brazilin had lower senescent cells compared to the untreated cells. The morphology of cells treated with IC50 (50μM) brazilin changed. The cells shape became rounded, cells were shrinkage and detached from the well plate, indicating that cells may undergo apoptosis. These results suggested that brazilin was cytotoxic towards T47D cells and its combination with dox potentially induced apoptosis and decreased cell senescence. The ability of brazilin to decrease cell senescence provides new insight of utilization of C. sappan or its constituents, particularly brazilin, as anti-ageing.
Woro Anindito Sri Tunjung, Vita Fatonah, Ghea Putri Christy, Sugeng Triono, Lisna Hidayati
Indonesian Journal of Pharmacy, Volume 31; doi:10.14499/indonesianjpharm31iss2pp61

Abstract:
Our previous study showed that kaffir lime leaf extracts may have anti-cancer properties. However, production of bioactive compounds is affected by environmental factors. Here, we present a method to control environmental conditions using in vitro culture techniques such as callus induction. Calluses were induced from seed embryo explants of kaffir lime on MS medium with combinations of 2,4-D and BAP at concentrations 1:0.5; 1:1; and 2:1, respectively. Fourty and 60 days-old calluses were extracted using chloroform and ethyl acetate and analyzed by GC-MS. Results showed all combinations of 2,4-D and BAP were able to induce callogenesis from seed embryo explants of kaffir lime with no significant differences of callus initiation time, biomass, morphology and growth rates. However differences were detected in the bioactive compound profiles. In kaffir lime callus, both fatty acids and secondary metabolites were detected. Specifically, in 40 days-old calluses (exponential growth phase) we detected α-pinene and 1.8–cineole in plants treated with 2,4-D: BAP at concentration 1:0.5 and 2:1. In 60 days-old calluses (stationary phase) we detected a number of compounds in plants treated with 2,4-D:BAP at concentrations of 1:0.5 and 2:1, including caryophyllene, linoleoyl chloride, thiogeraniol, stigmasterol, clianosterol, citronellal, neo-isopulegol, citronellol, geraniol, eugenol, cyclopropane, pristane, elemol and farnesol
Rachel Turalely, Mahardika Agus Wijayanti, Triana Hertiani, Musthofa Mustofa
Indonesian Journal of Pharmacy, Volume 31; doi:10.14499/indonesianjpharm31iss1pp51

Abstract:
Harmsiopanax aculeatus leaves, a medicinal plant with locally named kapur, have been used traditionally to treat malaria in Maluku, Indonesia. However, the scientific information of this plant is still limited. In our previous study, the methanol extract of this plant leaves have been proven to possess in vitro antiplasmodial activity. This study was conducted to evaluate in vitro antiplasmodial activity and cytotoxicity of subfractions of the plant leaves. Fractionation was performed using a column chromatography with Sephadex LH-20 as the stationary phase and methanol as the mobile phase. The subfractions obtained were then tested for in vitro antiplasmodial activity on a chloroquine-resistant FCR3 strain of Plasmodium falciparum using a visual method. Cytotoxicity was evaluated by using MTT assay. The in vitro antiplasmodial activity and cytotoxicity were expressed as IC50, calculated using probit analysis with SPSS 16 for windows. The results showed that the four subfractions tested have a high antiplasmodial activity with IC50 values of 0.09; 0.18; 0.01; and 0.77 µg.mL-1, respectively. In addition, these subfractions had IC50 values of >400 µg.mL-1 against Vero cells indicating that they were non-toxic. In conclusion, the subfractions of H. aculeatus leaves are very active and selective against P. falciparum. Further study will be conducted to isolate the active compounds.
Arman Rusman, Agung Endro Nugroho, Suwidjiyo Pramono
Indonesian Journal of Pharmacy, Volume 31; doi:10.14499/indonesianjpharm31iss1pp56

Abstract:
The Andrographis panicullata and Centella asistica extract have been reported that had a anti-diabetic effect. However, the specific mechanism and the effect combination of both were not yet reported. This study was purposed to determine the potency of extract, fractions and the combination of Andrographis panicullata (AP) and Centella asistica (CA) active fraction to inhibit alpha glucosidase enzymeand its ability to reduce DPPH radical.AP and CA were extracted using 50% ethanol then fractionated with solvents under different polarity levels. The inhibiting activity to alpha glucosidase enzyme and antioxidant activity of each fractions was tested. The most active fractions from AP and CA were then combined and re-tested for activity. The results result reported that both of AP and CA had inhibition of alpha glucosidase activity and antioxidant activity. Based on calculation combination index (CI) of of active fraction of AP and CA showing in alpha glucocidase activity had a antagonist action and antioxidant had a sinergic action. Therefore, combination of AP and CA not has not recomended for alpha glucocidase inhibitor but the combination has ability to reduce DPPH radical.
Roihatul Mutiah, Alfiyah Laily Inayatin, Rahmi Annisa, Yen Yen Ari Indrawijaya, Anik Listiyana
Indonesian Journal of Pharmacy, Volume 31; doi:10.14499/indonesianjpharm31iss1pp1

Abstract:
Chrysanthemum cinerariifolium (C.cinerariifolium) is a plant of the Asteraceae family, which has been applied by the community as an ornamental plant and traditional medicine. In this study, the effect of C. cinerariifolium leaves extract on inhibition of cell cycle and induction of apoptosis in T47D breast cancer cells was tested and compared to the standard chemotherapy agent. The citotoxic activity of C. cinerariifolium leaves extract against T47D cancer cells and Vero normal cells was tested by MTT method. Profile of apoptosis and cell cycle were observed by flow cytometry method. Based on chemical compounds profil which is tested used TLC showed that C.cinerariifolium leaves extracts contained flavonoid and terpenoid chemical compounds. The result of cytotoxic test showed that leaves extract of C. cinerariifolium was able to inhibit the growth of T47D cancer cell at IC50 418.8μg/mL. Doxorubicin, extracted from Streptomyces peucetius used as treatment in several cancers including breast cancer. Doxorubicin could inhibit the growth of T47D cancer cells in 115.1μg/mL. The results of cell cycle analysis showed that the C. cinerariifolium leaves extract inhibited cell cycle in G0-G1 and S phase, whereas doxorubicin was able to inhibit cell cycle in G0-G1 phase but experienced cell accumulation in G2-M phase. The percentage of apoptosis in cycle was showed in M1 (sub G1) and M5 (multinuclear) phase which treatment of C. cinerariifolium leaves extract was higher than doxorubicin. Therefore, C. cinerariifolium leaves extract has potential activity as anticancer agent causes inhibition of cell cycle and induction apoptosis.
Nur Rahmawati, Hariyanti Hariyanti , Fadlina Chany Saputri, Hayun Hayun
Indonesian Journal of Pharmacy, Volume 31; doi:10.14499/indonesianjpharm31iss1pp35

Abstract:
Two of Mannich bases derivatives of 4’-methoxy-substituted of asymmetrical cyclovalone analog (ACA) (2a and 2b) were synthesized. The synthesized compounds and the other two Mannich bases derivatives of 4'-methoxy-substituted ACA (2c and 2d) were evaluated for their in-vitro anti-inflammatory activity preliminary by protein denaturation inhibition method using a final concentration of 1.57 μM. The study found that all the Mannich bases exhibited anti-inflammatory potential with inhibition ranging from 33.17- 42.47%. The activity of 2b (42,47%) and 2d (41.90%) was higher than that of diclofenac sodium (35.27%) and the parent compound 1 (38.16%). As a conclusion, 2b and 2d have a prospect as a potential candidate for an anti-inflammatory agent. Further study should be done using more specific methods.
Quyen Thi Ngoc Phan, Van Thi Truong, Thanh Ngoc Pham, Ho Nhu Nguyen, Quynh Thi Huong Bui
Indonesian Journal of Pharmacy, Volume 31; doi:10.14499/indonesianjpharm31iss1pp42

Abstract:
Over-the-counter (OTC) cough and cold medications (CCMs) have been used to treat the symptoms of upper respiratory infection in children for decades. The safety of CCMs in children has been questioned. The data on knowledge of pharmacists in supplying cough medicines for children under two years have been limited. This study aimed to evaluate the pharmacists’ dispensing decisions to manage the cough in children under two years old. A descriptive cross-sectional was carried out in 300 pharmacies in 15 districts in Ho Chi Minh City, Vietnam. The pharmacists were interviewed by a simulated patient. The results showed that, information that pharmacists actively asked the client about the patient and disease symptoms was limited. Most pharmacists did not provide adequate instructions and counsel about using drugs for clients. Only 22/300 (7.33%) of pharmacists appropriately provided cough medicines for children under 2 years old. The main reason of inappropriateness was the deficiency of knowledge about updated contraindication of N-acetylcysteine (93.17%). Pharmacists in pharmacies located in districts 3, 11 and Binh Thanh had higher rate of rational provision than those in other districts. A good and full understanding of the patient symptom helped the pharmacists supply cough medicines more reasonably. The limited caution of pharmacists and the low proportion of pharmacists updating contraindication of N-acetylcysteine should be considered as a warning sign in pharmacy practice in Ho Chi Minh City, Vietnam.
Rina Herowati
Indonesian Journal of Pharmacy, Volume 31; doi:10.14499/indonesianjpharm31iss1pp27

Abstract:
Okra (Abelmoschus esculentus (L) Moench) fruit is empirically used in type 2 diabetes mellitus treatment. This research aims to know the antihyperglycemic activity of okra fruit extract and fractions in streptozotocin-nicotinamide (STZ-NA) induced as well as in insulin resistance diabetic rats, the effect on pancreatic cells regeneration, and the effect on immunohistochemical expression of glucose transporter-4. This study used a group of 35 male Wistar rats for STZ-NA induced diabetic model and another group of 35 rats for insulin resistance diabetic model. Gliclazide (0.72mg/kg BW) and metformin (45mg/kg BW) were used as drug control in STZ-NA induced and insulin resistance diabetes, respectively. Okra fruit ethanol extract, n-hexane, ethyl acetate, and water fraction were orally administered with dose of 200; 107; 6 and 86mg/kg BW, respectively, for 28 days after diabetic condition was obtained. Blood glucose level was measured every week. Hematoxylin-eosin staining was used to evaluate the pancreatic cells regeneration, while immunohistochemistry was used to evaluate the expression of glucose transporter-4 in muscle membrane cells, at the end of the treatment. The results revealed that ethyl acetate fraction was the most effective in lowering blood glucose level in both condition of diabetes. Ethyl acetate fraction decreased the necrosis of pancreatic cells in STZ-NA induced diabetic rats and increased the expression of glucose transporter-4 in muscle cell of insulin resistance diabetic rats.
Laela Hayu Nurani, Nurkhasanah Mahfudh, Ibnu Gholib Gandjar, Intan Rahayu
Indonesian Journal of Pharmacy, Volume 31; doi:10.14499/indonesianjpharm31iss1pp19

Abstract:
Cervical cancer can be treated conventionally with chemotherapy agents, but its use has side effects and complications in the form of damage to normal cells. This study aims to determine the potential of A. platensis as an alternative anticancer agent that is selective towards normal cells. Based on TLC analysis, A. platensis contains antioxidant compounds such as β-carotene, flavonoids, and terpenoids which are able to inhibit proliferation and trigger apoptosis of cancer cells. The study was conducted using cervical cancer cells HeLa and normal cells HDFa. A. platensis macerated with 96% ethanol at a ratio of 1:4. Based on probit analysis, it is known that ethanol extract of A. platensis has a cytotoxic effect on HeLa cells with IC50 values of 260.444μg/mL and index selectivity towards HDFa cells of 7.931. The mechanism of cytotoxic activity of ethanol extract of A. platensis is related to its ability to extend the doubling time, increase the induction of apoptosis, and reduce the rate of cells migration. Ethanol extract of A. platensis can also increase cells accumulation in the S phase to prevent cells from entering the G2/M phase.
Retno Murwanti, Azmi Rahmadani, Ritmaleni Ritmaleni, Adam Hermawan, Bambang Sulistiyo Ari Sudarmanto
Indonesian Journal of Pharmacy, Volume 31; doi:10.14499/indonesianjpharm31iss1pp11

Abstract:
Chemotherapy is the first-line treatment for triple-negative breast cancer (TNBC), yet toxicity and resistance effects have been the current problems. Curcumin,a natural compound, has been reported to exert anti-proliferative effects on various cancer cells, including breast carcinoma cells. However, the β-diketone moiety influences the stability of curcumin. Curcumin analogs, pentagamavunon-0 (PGV-0), and pentagamavunon-1 (PGV-1) were synthesized to improve the stability and activity of curcumin by modified the β-diketone moiety into mono-ketone pentanone. In this study, we evaluated the cytotoxicity, inhibition of cell cycle progression, and induction of apoptosis of curcumin and its analogs (PGV-0 and PGV-1) in murine triple-negative breast cancer 4T1 cell line. The cytotoxic evaluation was done by MTT assay, while apoptosis induction and cell cycle evaluation was performed by annexin V staining and detected by flow cytometry. Curcumin and its analogs, PGV-0, and PGV-1, significantly inhibit the viability of 4T1 breast cancer cells with an IC50 value of 34.34µg/mL, 13.76µg/mL and 38.21μg/mL, respectively. Apoptosis analysis with a dose of 10µg/mL and 15µg/mL in 4T1 breast cancer cells showed that curcumin and its analogs effectively induce apoptotic in a dose-dependent manner. In cell cycle analysis using a dose of 15µg/mL, curcumin inhibited the cell cycle progression in the S phase, whereas PGV-0 and PGV-1 inhibited the cell cycle in the G2/M phase. It could be concluded that curcumin analogs, PGV-0 and PGV-1, have higher potential to be developed as anti-cancer agents by inducing cell cycle arrest and apoptosis in triple-negative breast cancer.
Diani Mentari , Relita Pebrina, Diah Nurpratami
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 36-45; doi:10.14499/indonesianjcanchemoprev11iss1pp36-45

Abstract:
Fetal bovine serum (FBS) is a gold standard as a supplement to cell and tissue culture media. This is due to a large number of Growth Factor (GF) contained in FBS. However, the use of FBS is at risk of transferring endotoxins, prions, bacteria and viruses from animals to humans, so it is risky to be used on cell therapy. Human Platelet Lysate (HPL) is a medium that can be developed as an alternative cell growth medium. The advantage of HPL is that it does not contain aggregate platelets so it does not cause the cells to clot. This condition causes HPL to be used as a substitute medium replacing FBS for cell propagation. The use of HPL for cell propagation has been widely reported. However, the use of HPL in cancer cells has not been found. Thus, this study aims to see the effectiveness of HPL as a T47D cell culture medium. The study began with donor selection with criteria for the male sex, the blood type O, the age ≤35 years. Furthermore, the Platelet Concentrate (PC) was processed into HPL then measured pH, total protein and albumin levels. The cell viability was measured using the MTT assay to determine the ability of cell proliferation when propagation using HPL. The doubling time test was carried out as in the cell proliferation test. However, the incubation was carried out for 24 h, 48 h and 72 h and the HPL concentration used was 5%. The result shows that HPL 10% and 20% ability to increase proliferation better than the FBS 10%. HPL with a 5% concentration ability to shortens the doubling time than FBS 10% (doubling time is less than 19.94 h). It this study, cell proliferation is influenced by the pH of HPL and total protein but not by the amount albumin.Keywords: Human Platelet Lysate, Proliferation, T47D cell line, total protein, albumin.
Purwanto Purwanto , Sudibyo Martono
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 46-53; doi:10.14499/indonesianjcanchemoprev11iss1pp46-53

Abstract:
One of the main modalities of cancer treatment is chemotherapy, which uses chemicals that are generally electrophilic. These xenobiotic compounds sometimes does not produce effective response due to activity of glutathione S-transferase (GST) which inactivate the xenobiotics. Several natural phenolic compounds were reported to inhibit GST activity in vitro. Noni fruit (Morinda citrifolia L.) which contains flavonoids and other phenolic compounds such as scopoletin and morindon is proposed to interfere GST activity. This study aimed to analyze the effect of ethanolic extract of Noni fruit in vivo on GST activity in lung rat using 1,2-dichloro-4-nitrobenzene (DCNB). This substrate is a specific for class mu GST. First, rats were administered with ethanolic extract of Noni and dimethylbenz(α)anthracene (DMBA) for two weeks. The cytosolic fraction of lung was isolated then the GST activity was determined by simple kinetic program which was automatically calculated using spectrophotometer. The results showed that ethanolic extract of Noni in 1 and 5% (w/v) of concentration induced class mu GST activity, whereas 10% (w/v) of concentration inhibited class mu GST activity. After a treatment with DMBA, all tested concentrations of ethanolic extract of Noni inhibited class mu GST activity of lung rat significantly. These results indicated that Noni fruit extract can be further developed as a supportive agent of a chemotherapy drug.Keywords: DMBA, GST, Morinda citrifolia L., spectrophotometer.
Nur Dina Amalina, Meiny Suzery , Bambang Cahyono
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 1-6; doi:10.14499/indonesianjcanchemoprev11iss1pp1-6

Abstract:
Hyptis pectinata (L.) poit, popularly known in the world as “comb bushmint” is a medicinal plant commonly used for the treatment of throat and skin inflammations, bacterial infection, pain and cancer. The objective of this research is to determine the cytotoxic and antiproliferative effect under Hyptis pectinata ethanolic extract (HPE) treatment on breast cancer cells. The effect HPE of on cytotoxicity was examined by MTT assay on MCF-7 breast cancer cells. This assay also used to determine cell proliferation over 3 days of treatment with 1.5 – 100 µg/mL HPE. HPE showed that exhibited cytotoxic effects with IC50 value of 30 µg/mL for 24 hours and changes the physiological morphology on MCF-7 cells. Interestingly, the treatment of HPE for 48 and 72 hours highly decreases cell viability on MCF-7 with dose and time-dependent manner compared to untreated cells. These results indicate that HPE has antiproliferative activities and maybe the potential to be developed as a natural chemotherapeutic agent.Keywords: Hyptis pectinata (L.) poit extract, cytotoxicity, antiproliferative, MCF-7 cells
Ismanurrahman Hadi, Riris Istighfari Jenie, Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 7-15; doi:10.14499/indonesianjcanchemoprev11iss1pp7-15

Abstract:
TNBC, one of the sub type of breast cancers was widely known with high tumorigenic and poor prognosis than others. The development of combination agent (co-chemotherapy) with doxorubicin for chemotherapy of TNBC were carried out to decrease doxorubicin side effect and resistance in cancer. This present study aims to explore the co-chemotherapeutic properties of PGV-0 and investigate induction of doxorubicin on apoptosis, senescence and ROS against TNBC. 4T1 Cell line were used as a TNBC in vitro model. Cytotoxic measurement was performed using MTT assay resulting in IC50 values of 52 μM. Meanwhile, the combination of doxorubicin and PGV-0 showed synergistic effect which decreased cell viability of 4T1 better than single treatment of doxorubicin. Apoptosis analysis was performed using annexin V/PI assay indicated that the combination treatment of PGV-0 and doxorubicin increased apoptosis evidence. Senescence detection was carried out using senescence-associated-β galactosidase (SA-β-gal) assay. The results showed that a single treatment of PGV-0 induced cellular senescence and increased senescence cells in combination treatment. Moreover, DCFDA staining showed that PGV-0 increased ROS level at single treatment, whereas combination treatment increased ROS intracellular compared to the positive control of doxorubicin. Based on these results, PGV-0 has potential as a co-chemotherapeutic candidate on TNBC.Keyword: 4T1, PGV-0, Co-chemotherapy, Cytotoxic, Senescence, Apoptosis, ROS
Anif Nur Artanti, Umi Hanik Pujiastuti, Fea Prihapsara, Rita Rakhmawati
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 16-21; doi:10.14499/indonesianjcanchemoprev11iss1pp16-21

Abstract:
As one of the leading causes of death in worldwide, cervical cancer requires the effective therapies to reduce its mortality rate. One of the chemotherapy agents that frequently used in the treatment is cisplatin. However, due to drug resistance and its side effects, an agent that can be combined with cisplatin is needed. Parijoto fruit (Medinilla speciosa Reinw.ex.Bl) contains secondary metabolites compounds that have potential as anticancer. The study aims to determine the cytotoxic effect of methanol extract of Parijoto fruit calculated from the IC50 value and the synergicity of the combinational treatment with cisplatin evaluated from the Combination Index (CI) value and its cell viability by using MTT assay. Results showed that methanol extract of Parijoto fruit (MEP) performed cytotoxic effect on HeLa cell line with IC50 of 209.6 μg/mL while the value of IC50 of cisplatin against HeLa cells amounted to 12.8 μg/mL. The combination of 26.205 ppm (1/8 IC50) of MEP and 1.601 ppm (1/8 IC50) of Cisplatin performed synergistic effect on HeLa cell line with the CI value of 0.69. From the above results, it can be concluded that MEP is potential as co-chemotherapy agent based on the synergistic cytotoxicity effect with cisplatin.Keyword: cytotoxic, Medinilla speciosa, cisplatin, co-chemotherapy, MTT
Ivan Arie Wahyudi, Fahri Reza Ramadhan, Rama Insan Kusuma Wijaya, Retno Ardhani, Trianna Wahyu Utami
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 30-35; doi:10.14499/indonesianjcanchemoprev11iss1pp30-35

Abstract:
The utilization of natural resources, one of which is plants, has been researched as an alternative to synthetic drugs because of their natural content. Potato (Solanum tuberosum L.) peels, the parts of potatoes that are often cut off and discarded, have been reported to have some phenolic compounds and flavonoids in their composition. The extract of potato peels was investigated for its analgesic, anti-inflammatory, and anti-biofilm-forming properties. A hot plate test was conducted to assess the analgesic activity in treatment doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg with paracetamol as the reference drug and distilled water as the negative control, while carrageenan-induced paw edema was used to assess anti-inflammatory activity in treatment doses of 100 mg/kg, 200 mg/kg, and 400 mg/kg with diclofenac as the reference drug and distilled water as the negative control. Anti-biofilm-forming activity was tested by using the crystal violet assay. The results showed that, compared with the negative control, treatment doses of 100 mg/kg and 200 mg/kg significantly (p < 0.05) reduced pain stimuli, whereas a treatment dose of 100 mg/kg, 200 mg/kg, and 400 mg/kg significantly (p < 0.05) reduced the edema volume increment. However, compared with the positive control, paracetamol and diclofenac were associated with the least pain stimulus and the least edema volume increment, respectively. Potato peel extract against S. mutans biofilm formation demonstrated effectiveness (p < 0.05). Based on these data, it can be concluded that potato peel extract has analgesic, anti-inflammatory, and anti-biofilm-forming activities, as demonstrated in this study.
Rissa Laila Vifta , Fania Putri Luhurningtyas
Indonesian Journal of Cancer Chemoprevention, Volume 11, pp 22-29; doi:10.14499/indonesianjcanchemoprev11iss1pp22-29

Abstract:
Antioxidants are agents that can reduce free radicals. Parijoto fruit (Medinilla speciosa) contains flavonoids that could act as an antioxidant. However, those flavonoids are water-soluble and show low bioavailability. Nanotechnology is a potential approach to improve the bioavailability of flavonoids from Parijoto fruit. This study was conducted to determine the antioxidant activity of parijoto nanoparticles with variations of the chitosan, alginate, and chitosan/alginate encapsulants. Secondary metabolites of parijoto fruit were using the maceration method. The synthesis of parijoto nanoparticles was conducted using the ionic gelation method with chitosan, alginate, and chitosan/alginate encapsulation. Parijoto nanoparticle size and distribution were characterized using Particle Size Analyzer (PSA). The formation of nanoparticles in colloids was determined as a percent. The antioxidant activity of nanoparticle was evaluated using Ferric Reducing Antioxidant Power (FRAP) method using a UV-Vis spectrophotometer. Chitosan encapsulation produced nanoparticles with a size of 269.3 nm, pdI 0.372 and transmittance 99.379%. Alginate encapsulation produced a particle size of 366.4 nm, pdI 0.589 and transmittance 99.690%. The combination of chitosan/alginate encapsulants produced a particle size of 187.00 nm, pdI 0.239 and transmittance 99.894%. Parijoto nanoparticles obtained from chitosan, alginate, and chitosan/alginate encapsulant showed strong antioxidant powers indicated by IC50 values 2.442±0.047 ppm, 3.175±0.169 ppm and 2.115±0.045 ppm, respectively. Altogether, our study shows that parijoto nanoparticles are potent as antioxidant agents.Keywords: Alginate, antioxidant, chitosan, FRAP, Medinilla speciosa, nanoparticle
Muthi' Ikawati , Inna Armandari, Annisa Khumaira, Yogi Ertanto
Indonesian Journal of Pharmacy, Volume 30; doi:10.14499/indonesianjpharm30iss4pp260

Abstract:
The extract of Citrus reticulata has been studied for its biological activities, due to its citrus flavonoid content. The extract and its flavonoid compounds exhibit growth inhibition properties in several cancer cell lines and in vivo models. Conversely, the extract can also induce cell proliferation and angiogenesis, and shows estrogenic effects, in vitro and in vivo. Because of the contrasting effects that depend on the concentration or dosage, the precise action of the extract and its flavonoids need to be elucidated in various cell types. The objective of this study is to evaluate the effect of Citrus reticulata peel extract (Citrus extract) and hesperidin, a citrus flavonoid, on the modulation of cell proliferation in the RAW 264.7 macrophage cell line. Cell viability under Citrus extract or hesperidin treatment was assessed by using the MTT assay. The expression of interleukin-10 (IL-10), an anti-inflammatory cytokine, modulated by Citrus extract was also examined by immunostaining. Low concentrations of Citrus extract at 1 and 100 μg/mL were able to induce cell proliferation, though not significantly, as shown by cell viability of 138 and 114%, respectively. At higher concentrations of 500, 750, and 1000 μg/mL, Citrus extract decreased cell viability significantly by up to 64, 46, and 36%, respectively. Accordingly, hesperidin at low (3.1 μg/mL−61.1 μg/mL) or high (152.6 μg/mL−305.3 μg/mL) concentrations increased or reduced cell viability significantly by up to 116−136% or 10−61%, respectively. The value of the 50% inhibitory concentration (IC50) of Citrus extract was more than three times higher (756 μg/mL) than that of hesperidin (203 μg/mL = 332 μM). Additionally, 250 μg/mL of Citrus extract was able to induce IL-10 expression compared with the control. These results demonstrate that Citrus extract and hesperidin exert a biphasic effect on macrophage cells. The future development of Citrus extract as a co-chemotherapeutic, anticancer, or immunomodulatory agent should include careful consideration of its biphasic effect on each cell type.
Gregorius Bhaskara Wikanendra, Wawaimuli Arozal, Kusmardi Kusmardi, Vetnizah Juniantito, Andrea Laurentius
Indonesian Journal of Pharmacy, Volume 30; doi:10.14499/indonesianjpharm30iss4pp269

Abstract:
L-Citrulline shows potential activity as a supplement to prevent myocardial infarction through vasodilative and possible antioxidative effects but may be deleterious by causing nitrosative stress. This study determined the potentially deleterious effects of L-citrulline supplementation in isoproterenol-induced myocardial infarction with a focus on nitrosative stress. L-Citrulline supplementation was given orally at dosages of 300 or 600mg/kg body weight daily for 6 days. Myocardial infarction was induced in Wistar rats via subcutaneous injection of isoproterenol (85 mg/kg body weight (BW)) on day 4 and 5. Blood pressure was measured at the end of the study (day 6) and rats were sacrificed to collect heart tissue samples for a histopathological evaluation. The histopathological evaluation was done using hematoxylin and eosin staining for the myocardial damage evaluation and immunohistochemical (IHC) staining of arginase-2, inducible nitric oxide synthase (iNOS), and 3-nitrotyrosine to evaluate nitrosative stress. L-Citrulline supplementation failed to show a significant protective effect on blood pressure and exacerbated the decrease of diastolic blood pressure. Both low and high dose L-citrulline supplementation had a significant protective effect on myocardial damage compared to the isoproterenol group (p
Sudewi Mukaromah Khoirunnisa, Atika Dalili Akhmad
Indonesian Journal of Pharmacy, Volume 30; doi:10.14499/indonesianjpharm30iss4pp309

Abstract:
The high prevalence of hypertension in Indonesia, encourages studies related to how the quality of life of patients with hypertension. The purpose of this study was to measure quality of life, identify and explain factors related to the quality of life of patients with hypertension.The study design was descriptive correlation using a cross sectional study approach. The study subjects were all outpatient hypertensive patients several health centers in Bandar Lampung. The instrument used in this study was the Indonesian SF-36. The data collected included the patient's demographic characteristics including gender, age, education, occupation, and marital status, and the fields related to the health history of the study subjects included the duration of hypertension, complications, and the number of antihypertensive drugs consumed. Data were analyzed using bivariate analysis to see the relationship between two variables with the level of significance used was 5% (α = 0.05) with the value of the confidence interval set was 95%. Multivariate analysis was conducted to study the relationship of several independent variables with one or several dependent variables.The results of univariate analysis showed that age, marital status, duration of illness, complications, and the number of drugs consumed had an effect on the quality of life of hypertensive patients (p
Teguh Hari Sucipto, Yovilianda Maulitiva Untoro, Harsasi Setyawati, Anisa Maharani, Novia Faridatus Sholihah, Siti Churrotin, Ilham Harlan Amarullah, Soegeng Soegijanto
Indonesian Journal of Pharmacy, Volume 30; doi:10.14499/indonesianjpharm30iss4pp316

Abstract:
Dengue virus (DENV) serotypes DENV-1 to DENV-4 are enveloped viruses that belong to the genus Flavivirus of the Flaviviridae. Dengue vaccine or antiviral has not yet been clinically approved for humans, even though there have been great efforts toward this end. Antiviral activity against DENV is needed to develop to be an alternative drug for DENV virus. Cobalt(II) chloride have been used in the treatment and prevention of diseases of humans since ancient times. The aim of this study is to investigate the antiviral effects and Cytotoxicity of Cobalt(II) chloride. This compound was further investigated for its inhibitory effect on the replication of DENV-1 in Vero cells. Antiviral activity and Cytotoxicity measured by WST-1 assay. The IC50 value of the Cobalt(II) chloride for DENV-1 was 0.38 μg/ml. The cytotoxicity of Cobalt(II) chloride to Vero cell suggest that the CC50 value was 2.91 µg/ml The results of this study demonstrate the anti-dengue serotype 1 inhibitory activity of Cobalt(II) chloride was a high toxic compound.
Badrunanto Badrunanto, Wulan Tri Wahyuni, Mohamad Rafi
Indonesian Journal of Pharmacy, Volume 30; doi:10.14499/indonesianjpharm30iss4pp301

Abstract:
A new simple and effective routine analytical method for quantification of curcuminoids in Curcuma xanthorrhiza was developed by high-performance liquid chromatography. This method based on chromatographic fingerprint combined with a quantitative analysis of multi-components by single marker (QAMS). Curcumin was selected as an internal marker for the determination of two other similar compounds, i.e. bisdemethoxycurcumin and demethoxycurcumin, by using the relative coefficient factor (RCF). Excellent linearity was obtained for each component (r2 > 0.9998), and the recovery of extraction methods were within 100.23-103.95%. The precision of the method was good at inter-day and intra-day analysis (RSD < 4.0%). The stability of RCFs was good under various chromatographic conditions with RSD < 1%, and the ratio of retention time was used to locate each compound. The quantification of curcuminoids between QAMS and external standard method (ESM) proved the consistency and similarity of the two method (RSD < 2%). This study demonstrated that QAMS could be used as a routine method for quality control of curcuminoids in C. xanthorrhiza. This method successfully proved accurate, stable, more effective and simple than external standard method.
Sonia Meta Angraini, Nadzifa Nugraheni, Edy Meiyanto, Adam Hermawan
Indonesian Journal of Cancer Chemoprevention, Volume 10, pp 114-121; doi:10.14499/indonesianjcanchemoprev10iss3pp114-121

Abstract:
Senescence defined as an irreversible cell cycle arrest. Senescence can inhibit cancer growth and suppress the progression of cancer. Some anticancer compounds are known to have the potential to induce senescence. Senescence defence against tumor development by preventing proliferation of cells with DNA damage. The study aimed to determine the cytotoxic effects and senescence induction of Pentagamavunon-0 (PGV-0) on Human Epidermal Growth Factor Receptor 2-positive (HER2-positive) breast cancer cells, HCC 1954. Cytotoxic tests carried out with 3- (4.5-dimethylthiazzol-2yl) -2.5-tidiphenyltetrazolium (MTT) assay showed that PGV-0 exhibited a strong cytotoxic effect with a the half maximal inhibitory concentration (IC50) value of 39 μM. Treatment with IC50 in sub-doses combined with doxorubicin showed cytotoxic enhancement effects. The senescence assay using SA-β-Galactosidase showed that the PGV-0 in a single treatment was able to induce senescence with a percentage of cell senescent of 15%. The combination treatment of PGV-0 at the half dose of IC50 with doxorubicin 100 nM was able to induce senescence with the percentage of senescent cells of 25%. Moreover, PGV-0 also increased intracellular reactive oxygen species (ROS). The results of this study indicate that PGV-0 exhibits cytotoxic effect, increases cytotoxic effect of doxorubicin and induces senescence that may correlate to the increasing of intracellular ROS in 1954 HCC cells.Keywords: Pentagamavunon (PGV-0), HCC 1954, Cytotoxic, Senescence
Desak Gede Sri Andayani, Puspa Dewi Narrij Lotulung, Anny Sulaswaty, Nur Qaanitaati, Desak Gede Tirta Andini, Rahmaniar Mulyani, Eva Nursyifa
Indonesian Journal of Cancer Chemoprevention, Volume 10, pp 159-168; doi:10.14499/indonesianjcanchemoprev10iss3pp159-168

Abstract:
Fragaria x ananassa (strawberry) is a subtropical plant that can adapt well in tropical highlands. Fragaria x ananassa have been widely used to cope with health problems. The active compound component of secondary metabolites contained in Fragaria x ananassa has the potential as an antioxidant. This research is done to isolate secondary metabolites from extract of Fragaria x ananassa fruits. Extract Fragaria x ananassa was produced by maceration using ethanol as the solvent. Separation and isolation compound were carried out using Vacuum Liquid Chromatography (VLC) and Gravity Column Chromatography (GCC) guided by Thin Layer Chromatography (TLC) using hexane: ethyl acetate (3:7) as the eluent. The flavonoid compound was determined by the total content of phenolic and flavonoid in extract of Fragaria x ananassa fruits. The results of total phenolic content and total flavonoid content were 0.1130 mg/g and 0.0112 mg/g, respectively. The alkaloid compound was determined by Dragendorff testing. The elucidation of the structure by Fourier Tansform Infrared (FTIR), Nuclear Magnetic Resonance (NMR), and Liquid Chromatography Mass Spectrometry (LCMS) showed that the active compound contained in the secondary metabolite of extract ethanol from Fragaria x ananassa is 3-Cyclopentyl-5-(1-hydroxyethyl)-1,6-dihydro-7H-pyrazolo[4,3- d]pyrimidin-7-one.Keywords: Fragaria x ananassa extract, flavonoid, alkaloid, total phenolic and flavonoid content, FTIR, NMR, LCMS.
Roihatul Mutiah, Trian Sidha Minggarwati, Risma Aprinda Kristanti, Erna Susanti
Indonesian Journal of Cancer Chemoprevention, Volume 10, pp 131-139; doi:10.14499/indonesianjcanchemoprev10iss3pp131-139

Abstract:
Eleutherine palmifolia (L.) Merr. is a typical plant found in Central Kalimantan that has been used empirically by the Dayak people as medicine for various diseases, including cancer. The plant contains flavonoid compounds that potentially used as an anticancer. The purpose of this study is to find the most active fraction, indicated by its cytotoxic potency on HeLa cervical cancer cell line, and to identify compounds in E. palmifolia bulbs fraction. E. palmifolia bulbs was extracted by maceration. The extraction with ultrasonic bath and partition fractionation was conducted by using n-hexane, chloroform, and ethyl acetate. Each fraction was tested for toxicity level on HeLa cells using MTT assay. The identification of active compounds was carried out by Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS). The result showed that based on the IC50 value, the ethyl acetate fraction had the highest bioactivity. IC50 values of n-hexane, chloroform, and ethyl acetate fractions were 250.77±19.01; 720.46±42.38; and 44.34±9.45μg/mL, respectively. The identification of the active compound in ethyl acetate fraction resulted 28 chemical compounds. Compounds with the highest percentage area were isoliquiritigenin and oxyresveratrol. The ethyl acetate fraction of E. palmifolia bulbs is potential to be developed as an anticancer candidate (phytopharmaceutical).Keywords: Compound identification, Anticancer activity, Eleutherine palmifolia (L.) Merr., cervical cancer
Akrom Akrom , Titiek Hidayati, Sagiran Sagiran, Indrayanti Indrayanti
Indonesian Journal of Cancer Chemoprevention, Volume 10, pp 140-148; doi:10.14499/indonesianjcanchemoprev10iss3pp140-148

Abstract:
Interferon-gamma (IFN-γ) is one of the central cytokines in the anti-carcinogenesis immune response. Black cumin seeds (BCS) have an active content of thymoquinone and unsaturated fatty acids with biological activity as immunomodulators. This study aimed to determine the effect of administration of BCS extract on IFN-γ secretion activity by DMBA-induced SD rat lymphocytes. In vivo experimental study on DMBA-induced SD rats, BCS extract was given with three doses for two weeks before being induced and five weeks during DMBA induction. IFN-γ levels in lymphocyte culture supernatants were determined by the ELISA method. The difference in IFN-γ levels between groups was analyzed by ANOVA test, the significance of 95%. The results showed that administration of BCS extract for 14 days did not affect cellular composition toward the edge of the test animal. BCS extract can increase IFN-γ secretion activity by DMBA-induced SD rat lymphocytes.Keywords: black cumin seed, IFN-γ; DMBA: immunomodulator, carcinogenesis.
Haruma Anggraini Muflikhasari, Riris Istighfari Jenie, Ratna Asmah Susidarti, Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention, Volume 10, pp 149-158; doi:10.14499/indonesianjcanchemoprev10iss3pp149-158

Abstract:
Pentagamavunone-0 (PGV-0), one of the curcumin analogue, is reported to have a cytotoxic effect on various cancer cells. This study aimed to explore the growth inhibitory effects of PGV-0 against highly-metastatic breast cancer, 4T1 cells under stress condition covering 2D and 3D speroid cytotoxic, anti-migration, and suppression of MMP-9. PGV-0 showed cytotoxic effects on 2D and 3D 4T1 cells with IC50value of 49 μM and 26 μM, respectively. In addition, PGV-0 performed anti-migratory effect. The single treatment at 25 μM PGV-0 and 50 μM showed inhibitory effect on cell migration by 54% and 51% respectively. whilst, the combination of PGV-0 at the concentration of 25 μM and 50 μM with doxorubicin significantly inhibited cell migration by 41% and 38%, respectively. The gelatin zymography assay showed that PGV-0 decreased MMP-9 expression both in a single treatment and in combination with doxorubicin. In conclusion, PGV-0 is potential to be developed as anti-tumorigenesis agent on highly-metastatic breast cancers.Keywords: Pentagamavunone-0 (PGV-0), anti-migration, MMP-9, 4T1 cells, spheroid
Indonesian Journal of Cancer Chemoprevention, Volume 10, pp 122-130; doi:10.14499/indonesianjcanchemoprev10iss3pp122-130

Abstract:
Proto-oncogene tyrosine-protein kinase Src is also known as simply Src is a tyrosine kinase protein which is one of the targets in various cancer therapies such as leukemia. Meanwhile, akar kuning (Arcangelisia flava) has gained significant attention as a medicinal plant that has a cytotoxic effect on various types of cancer cells. This study aims to determine the potential of secondary metabolites of akar kuning as Src inhibitors. Molecular docking was carried out using Autodock Vina 1.1.2 with 2HCK receptors, that quercetin and dasatinib were used as reference ligands. The docking results showed that the highest affinity was shown by berberine with a ΔG value of -9.0 kcal/mol, exceeded quercetin and dasatinib. However, the highest amino acid similarity to quercetin and dasatinib was produced by jatrorrhizine, with 93.33% and 73.91%, respectively. Interestingly, berberine is the ligand with the third-highest similarity after jatrorrhizine and palmatine, while jatrorrhizine has the second-highest affinity after berberine. The results concluded that the combination of berberine and jatrorrhizine is predicted to be optimally used as an Src inhibitor in cancer therapy.
Nanda Ayu Puspita, Hasen Alhebshi
Indonesian Journal of Pharmacy, Volume 30; doi:10.14499/indonesianjpharm30iss4pp241

Abstract:
Objective: To investigate the effect of Phyllanthus niruri Linn (Euphorbiaceae) in the proliferation of human leukemic cells (MOLT-4 and K562).Methods: Phyllanthus niruri L (P.niruri) was macerated by using various solvents to obtain the crude extracts. Cytotoxicity of the extracts against MOLT-4 and K562 cells was tested using MTT assay to find the IC50 value. To analyse cell cycle progression, cellular DNA was measured using propidium iodide (PI) staining. Apoptosis induction was evaluated using Annexin V-FITC and PI staining and analysed using FACSVerse flow cytometry. Finally, the expression of p53 on MOLT-4 and K562 cell lysate was measured by western blotting, to identify the possible mode of action of the anticancer activity.Results: P. niruri crude extracts demonstrated a potential anti-cancer effect towards MOLT-4 cells (IC50 range was 42.21 ± 4.98 to 97.06 ± 18.29 µg/ml). However, against K562 cells, P.niruri extracts exhibited a lower inhibitory potency (the IC50 was 120.19 ± 8.48 to 256.55 ± 26.22 µg/ml). The results showed the selectivity of the toxic effect of the extracts against MOLT-4 and K562. To evaluate the possible mechanism of action the anticancer effect, we evaluated P. niruri extract action in apoptosis induction and p53 expression. The results showed that methanol and hexane extract inhibited MOLT-4 cell progression from G1 to S-phase, indicating G1 cell arrest. Moreover, apoptotic cell population following treatment of MOLT-4 and K562 cells with methanol extract was markedly increased, showing morphological signs of apoptosis including membrane degradation and chromatin condensation. Furthermore, we found that there was an increase in p53 expression following MOLT-4 treatment with methanol extract, suggesting that p53 induction may be involved in cell apoptosis.Conclusions: The results indicated the involvement of p53 pathway in the mechanism of anti-cancer activity exerted by P. niruri extract on MOLT-4 cells. However, for cancer cells lacking P53 expression, such as K562 cells, apoptosis might take place via other pathways.
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