Indonesian Journal of Cancer Chemoprevention

Journal Information
ISSN / EISSN : 2088-0197 / 2355-8989
Current Publisher: Indonesian Society for Cancer Chemoprevention (10.14499)
Total articles ≅ 191
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Puguh Indrasetiawan, Sari Haryanti, Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention, Volume 11; doi:10.14499/indonesianjcanchemoprev11iss3pp168-186

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

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
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

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
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

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

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

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
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

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
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

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

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

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.
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