Journal Indonesian Journal of Cancer Chemoprevention

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Yonika Arum Larasati, Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention, Volume 9, pp 47-62; doi:10.14499/indonesianjcanchemoprev9iss1pp47-62

Abstract:Cinnamon (Cinnamomum spp.), an ancient spice, has been explored as a potential for medicinal purposes. Despite numerous studies about its potency in overcoming of numerous diseases, the potency as anti-cancer would be a challenge. This current article provides a review of the anti-cancer and chemoprevention potency of cinnamon and its major constituents: cinnamaldehyde, cinnamic acid, 2-hydroxycinnamaldehyde, 2-methoxycinnamaldehyde, and eugenol. Comprehensively, cinnamon and its constituents exhibit the anti-cancer and cancer prevention activities through various mechanisms: (1) anti-proliferation, (2) induction of cell death, (3) anti-angiogenesis, (4) anti-metastasis, (5) suppression of tumor-promoted inflammation, (6) immunomodulation, and (7) modulation of redox homeostasis; both in vitro and in vivo. Moreover, cinnamon also shows the synergistic anti-cancer effect with well-known anti-cancer drugs, such as doxorubicin, which support its potency to be used as a combination chemotherapeutic (co-chemotherapeutic) agent. However, further study should be established to determine the exact target molecule(s) of cinnamon in the cancer cells.Keywords: cinnamon, spice, cancer, anti-cancer, chemopreventive
Muthi Ikawati, Endah Puji Septisetyani
Indonesian Journal of Cancer Chemoprevention, Volume 9, pp 23-31; doi:10.14499/indonesianjcanchemoprev9iss1pp23-31

Abstract:The use of 5-fluorouracil (5-FU) in colon cancer as the primary chemotherapy has not been meet satisfactory effectiveness. Therefore, the development of new chemicals as a chemopreventive agent and a combination agent (co-chemotherapeutic agent) for colon cancer is important. Pentagamavunone-0 (2,5-bis-(4'-hydroxy-3'-methoxybenzylidine) cyclopentanone) (PGV-0), one of curcumin analogs, exhibits cytotoxic effect and apoptosis induction in various cancer cell lines, including colon cancer cell, better than curcumin. This study aimed to investigate the cytotoxic potency of PGV-0 in combination with 5-FU and their effects, in single or in combination, on cell cycle toward WiDr colon cancer cell line. The cells were treated with combination concentrations of PGV-0 and 5-FU, and examined by MTT cell viability assay. The value of combination index (CI) as a parameter of cytotoxic combination assay was measured by a combination index method. Cells were stained with propidium iodide and the cell cycle distribution was determined by flowcytometry. CI calculation showed additive effects between PGV-0 and 5-FU. Combination of PGV-0 and 5-FU gave synergism on cell cycle. Single treatment of PGV-0 increased apoptosis, illustrated as subG1-phase accumulation, stronger than single treatment of 5-FU. Meanwhile, combination of PGV-0 and 5-FU demonstrated S-phase arrest. Based on these results, it can be concluded that PGV-0 has the potential to be developed as a co-chemotherapeutic agent for colon cancer but still requires further tracking of its molecular mechanisms.Keywords: Pentagamavunone-0 (PGV-0), 5-fluorouracil (5-FU), colon cancer,combination, cell cycle
Laili Nailul Muna, Riris Istighfari Jenie
Indonesian Journal of Cancer Chemoprevention, Volume 9, pp 9-15; doi:10.14499/indonesianjcanchemoprev9iss1pp9-15

Abstract:One of the efforts to cure breast cancer is a combination of the chemotherapeutic agent with medicinal plants. This study was conducted to examine the activity of the combination between doxorubicin, curcuma rhizome (Curcuma xanthorriza Roxb.) ethanolic extract (CEE), and awar-awar leaves (Ficus septica Burm.f.) ethanolic extract (AAE) in inducing apoptosis and modulating the cell cycle progression in breast cancer T47D cells. The combination activity was performed using three series of concentration, 1/3; 1/6 and 1/12 of IC50, The combination index (CI) of doxorubicin, CEE and AEE was determined under MTT assay. The result showed that the combination of 10 µM, 5 µg/ml, 1 µg/ml concentrations of doxorubicin, CEE and AEE respectively result in synergistic effect with CI values less than 1. The treatment exhibited the cell accumulation in S phase (27.7%) against T47D breast cancer cells confirmed through cell cycle examination by flow cytometry. These results provided the evidence that CEE and the AEE can be developed as co-chemotherapeutic agents combined with doxorubicin to improve the effectiveness of breast cancer treatment.Keywords : Curcuma xanthorriza Roxb., Ficus septica Burm.f., doxorubicin, cell cycle.
Ika Nurzijah, Dina Ratna Juwita
Indonesian Journal of Cancer Chemoprevention, Volume 9, pp 41-46; doi:10.14499/indonesianjcanchemoprev9iss1pp41-46

Abstract:Clonorchiasis is a parasitic infection caused by food borne trematode, Clonorchis sinensis that is mainly prevalent in Asian countries, including South Korea, China, northern Vietnam, Japan, as well as far-eastern Russia, in which over 35 million people are the casualties. Clonorchiasis is characterized by the development of hepatic fibrosis. Upon chronic liver injury following the C. sinensis infection, hepatic fibrosis develops into cholangiocarcinoma with a concomitant genetic and epigenetic mutations. Cholangiocarcinoma represents important clinical manifestation of C. sinensis infection and causes high rate of morbidity. TGF- β/Smad signalling is known to initiate hepatic fibrosis following the hepatic injury. However, little is known about the role of TGF- β/Smad signalling during C. sinensis induced hepatic injury and the underlying contribution of TGF- β/Smad signalling in the development of cholangicarcinoma. The expression dynamic of TGF-β/Smad signalling and their role in the development of hepatic fibrosis in C. sinensis infected BALB/c mice have been investigated. Concomitantly but irrespective to C. sinensis infection, the role of hepatic epithelial TGF-β during hepatic fibrosis and the development of cholangiocarcinoma arising from hepatic epithelial cells have also been dissected. Both findings will be reviewed in this paper. Thereby, the link between TGF-β/Smad signalling, hepatic fibrosis during C sinensis infection, and cholangiocarcinoma could be drawn clearly.Keywords: Clonorchis sinensis, TGF-β/Smad signalling, Hepatic fibrosis, Cholangiocarcinoma
Nindi Wulandari, Argandita Meiftasari, Hilyatul Fadliyah, Riris Istighfari Jenie
Indonesian Journal of Cancer Chemoprevention, Volume 9, pp 1-8; doi:10.14499/indonesianjcanchemoprev9iss1pp1-8

Abstract:Doxorubicin is a chemotherapeutic agent that causes a lot of side effects in high doses. Thus, combination with a co-chemotherapeutic agent which can increase its toxicity on cancer cells, is needed to reduce its therapeutic dose. Red betel leaves (Piper crocatum Ruiz & Pav.) have been known to contain flavonoids and alkaloids that have anticancer activity. This study was conducted to determine the cytotoxic effect and apoptosis induction of red betel leaves methanolic extract (RBM), doxorubicin (dox) and the combination of them on WiDr cells as model of colon cancer. RBM was extracted by soxhlet method using methanol. Cytotoxicity assay was performed using MTT assay for both single and combination treatments for 24 hours to determine IC50 and CI as their parameters. Apoptosis induction was analyzed by double staining method using ethidium bromide-acridine orange staining. Treatment of RBM and dox on WiDr cells for 24 hours showed cytotoxic activity with IC50 100 μg/mL and 1.6 μM respectively. Combination of RBM and dox performed synergism effect with CI
Rohmad Yudi Utomo, Annisa Novarina, Prisnu Tirtanirmala, Ria Fajarwati Kastian, Riris Istighfari Jenie
Indonesian Journal of Cancer Chemoprevention, Volume 9, pp 32-40; doi:10.14499/indonesianjcanchemoprev9iss1pp32-40

Abstract:Combination chemotherapy (co-chemotherapy) is a recent strategy to reduce the toxicity effect and increase the effectivity of chemotherapeutic agent, such as Doxorubicin (Dox). Caesalpinia sappan L. are potential to be developed as co-chemoterapeutic agents due to its strong cytotoxicity toward several breast cancer cells. The purpose of this research is to observe the cytotoxicity of Brazilein containing fraction (BCF) in single and its combination with doxorubicin on T47D cells. BCF was obtained by fractionation using chloroform:ethyl acetate (40:60 v/v) as mobile phase. Molecular docking results showed that Brazilein and Brazilin interacted with Bcl-2 with different binding properties. Based on MTT assay, Dox and BCF performed potent cytotoxicity with IC50 value of 403 nM and 68 μg/mL, respectively. BCF increased the cytotoxicity of Dox and performed synergism with CI value 1. Under Annexin V PI staining Flowcytometry, BCF in single and its combination with doxorubicin induced apoptosis. In conclusion, single treatment of BCF and its combination with Dox performed cytotoxic effect and induced apoptosis on T47D cell lines.Keywords: Brazilein containing fraction, Doxorubicin, Co-chemoteraphy, Apoptosis, T47D cells
Dhania Novitasari, Sri Handayani, Riris Istighfari Jenie
Indonesian Journal of Cancer Chemoprevention, Volume 9, pp 16-22; doi:10.14499/indonesianjcanchemoprev9iss1pp16-22

Abstract:Many natural products have been widely explored for their pharmacological activities, including anticancer activity. Hedyotis corymbosa L. is known for its anticancer properties toward several cancer cell lines. The study aims to investigate whether ethanolic extract of Hedyotis corymbosa L. (EEH) performs anticancer properties by inhibiting migration and metastasis on breast cancer cells. Cytotoxic evaluation by using MTT assay was carried out to determine EEH effect on 4T1 breast cancer cells, meanwhile to investigate the treatment of EEH in migration and metastasis inhibitory effect, scratch wound healing assay and gelatin zymography were conducted in this study. The data showed that EEH possessed cytotoxic activity with IC50 value of 400 μg/mL. Interestingly, migration inhibitory effect was shown up to 42 hours and the activity of MMP-9 was also decreased after the treatment with EEH. According to these findings, we suggest that Hedyotis corymbosa L. promotes another anticancer properties by inhibiting migration and metastasis towards breast cancer cells.Keywords : Hedyotis corymbosa L., cytotoxicity, migration, metastatic, 4T1 breast cancer cells
Asri Mega Putri, Nindya Budiana Putri, Rahmawaty Rachmady, Idlohatud Dilalah, Retno Murwanti, Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention, Volume 8, pp 126-134; doi:10.14499/indonesianjcanchemoprev8iss3pp126-134

Abstract:Antioxidants have the ability to scavenge free radicals, leading to inhibition of cells senescence. Secang Heartwood (Caesalpinia sappan L.) contains flavonoid brazilein, known of its high antioxidant activity. However, the activity of secang as senescent cells inhibitor has not been known. The aim of this study is to explore the potential of Caesalpinia sappan ethanolic extract (CSE) as free radical scavenger, thus inhibits senescent cells. Two concentrations of SE under IC50, 2µg/mL, 5µg/mL and 10µg/mL were applied on Mesenchymal Stem Cells (MSCs) and combined with 5µM of doxorubicin (Dox) as senescence inductor; both of them were compared with MSCs-Dox group. X-gal, chromogenic substrate of senescent cells, was given on MSCs, giving blue stain on senescent cells. To explore brazilein mechanism in senescence inhibition, molecular docking using PLANTS on topoisomerase II was performed. MSCs that treated with 10µg/mL of SE qualitatively showed reduction intensity of blue stain. Number of stained cells also reduced from 76% of MSCs-Dox to 38 % of 10µg/mL SE-Dox group. Docking score shows that brazilein (-86.91) is more stable to interact with topoisomerase II than doxorubicin (-82.46) and has same binding site (Val 174). These findings demonstrate starting knowledge on CSE potential as senescent cells inhibitor through brazilein activity on topoisomerase II.Keyword: Caesalpinia sappan L., Senescence, β-galactosidase, Molecular Docking
Meirizky Zulharini, Ika Rahmawati Sutejo, Hilyatul Fadliyah, Riris Istighfari Jenie
Indonesian Journal of Cancer Chemoprevention, Volume 8, pp 94-100; doi:10.14499/indonesianjcanchemoprev8iss3pp94-100

Abstract:Breast cancer is one type of cancer with a high mortality rate due to its metastatic property. Red betel leaves (Piper crocatum Ruiz dan Pav) has been known as herbal medicine containing biophenolic, such as apigenin and luteolin derivatives which has cytotoxic activity toward cancer cells. This study is intended to explore the inhibitory effect of Piper crocatum leaves methanolic extract (PCM) on cell proliferation and migration by using 4T1 cells as model of metastatic breast cancer. By using MTT assay, PCM performed cytotoxic activity in a dose dependent manner with IC50 value of 120 μg/mL. Wound healing assay revealed that migration inhibitory activity of PCM on 4T1 cells at the concentration of 30 µg/mL. In conclusion, PCM perform cytotoxic effect and antimigration activity toward metastatic breast cancer cells.Keywords : breast cancer cells, Piper crocatum Ruiz & Pav, cytotoxic, cell mgration
Devi Nisa Hidayati, Riris Istighfari Jenie, Edy Meiyanto
Indonesian Journal of Cancer Chemoprevention, Volume 8, pp 120-125; doi:10.14499/indonesianjcanchemoprev8iss3pp120-125

Abstract:Curcuma (Curcuma xanthorriza Roxb.) and Awar-awar ((Ficus septica Burm.f.) are well known to have anticancer potential especially for breast cancer with low toxicity. This study aims to examine the potential effect of the combination of Curcuma ethanolic extracts (CEE) and awar-awar leaves ethanolic extract (AEE) to increase the efficacy of cisplatin toward T47D breast cancer cells. The combination activity was done using 3 series of concentration, 1/3; 1/6 and 1/12 of IC50, to determine the combination index (CI) of cisplatin, CEE and AEE under MTT assay. The result showed that the combination of 2.5 µM, 5 µg/ml, 1 µg/ml concentrations of cisplatin, CEE and AEE respectively result in synergistic effect with CI values less than 1. The treatment exhibited the cell accumulation in S phase (27.7%) against T47D breast cancer cells confirmed through cell cycle examination by flow cytometry. These results provided the evidence that the CEE and the AEE can be developed as co-chemotherapeutic agents combined with cisplatin to improve the effectiveness of breast cancer treatment.Keywords : Curcuma xanthorriza Roxb., Ficus septica Burm.f., cisplatin, cell cycle
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