Doxorubicin is one of the chemotherapy agents that is often used in breast cancer therapy. Phenomenon of breast cancer cell resistance to chemotherapy agents has been traced to the molecular level. The development of compounds that can overcome drug resistance chemotherapy needs to be continuously developed, especially agents with specific molecular targets, namely P-glycoprotein (Pgp), NFkB, cyclin, and cyclin-dependent kinase (CDK). Another alternative is the combination of chemotherapy agents with chemopreventive agents (co-chemotherapy) to reduce side effects and increase sensitivity of cancer cells. Doxorubicin is often used in breast cancer therapy. This study was performed to determine the effect of ethanolic extract of Pinang Masak Jambi (Areca catechu L.) (EEPMJ) and doxorubicin combination on MCF-7 breast cancer cells. Cytotoxic assay of EEPMJ and doxorubicin, alone, or in combination, was done using MTT test method to determine the IC50 and CI (Combination Index) values. The results indicated that EEPMJ and doxorubicin had IC50 values of 75.1 µg/ml and 22 µg/ml, respectively. Based on CI values, all combination concentration showed varying CI values. The concentration of 1/8 IC50 of EEPMJ with 1/2, 1/4, and 1/8 IC50 of doxorubicin showed a strong synergistic effect (CI 0.1 - 0.3), with the inhibition of cell viability up to 67.39%. This synergistic effect occurs because EEPMJ potentially could increases the cytotoxicity of doxorubicin.
American Cancer Society. (2018). Cancer Facts & Figures 2018, US, American Cancer Society.
The Jakarta Breast Cancer Foundation Dharmais Hospital. Chou, T. C. (2010). Drug Combination studies and their synergy quantification using the Chou-Talalay method. Cancer Research, 70(2), 440-447.
El-Sayyad, H. I., Ismail, M. F., Shalaby, F. M., Abou-El- Magd, R. F., Gaur, R. L., Fernando A., Raj, M. H. G., & Ouhtit, A. (2009). Histopathological effects of cisplatin, doxorubicin and 5-flurouracil (5-FU) on the liver of male albino rats. International Journal of Biological Sciences, 5(5), 466-473.
Ferguson, P.J., Kurowska, E., Freeman, D.J., & Koropatnick, D.J. (2004). A flavonoid fraction from cranberry extract inhibits proliferation of human tumor cell lines, Journal of Nutrition, 134, 1529-1535.
Globocan. (2012). Estimated cancer incidence, mortality and prevalence worldwide in 2012. France: WHO.
Han, X., Pan, J., Ren, D., Cheng, Y., Fan, P., & Lou, H. (2008). Naringenin-7-O-Glucoside Protects Againts Doxorubicin-Induced Toxicity In H9c2 Cardiomyocytes by Induction of Endogenous Antioxidant Enzymes. Food and Chemical Toxicology, 46 (9), 3140-3146.
InfoDATIN. (2016). Months of caring breast cancer. Jakarta: Ministry of Health Indonesian, The Center of Data and Communication.
Kwan, Y. P., Saito, S. T.., Ibrahim, D., Al-Hassan, F. M. S.,., Oon, C. E.., Chen, Y., Jothy, S. L.., Kanwar, J. R., & Sasidharan, S. (2016). Evaluation of the cytotoxicity, cell-cycle arrest, and apoptotic induction by Euphorbia hirta in MCF-7 breast cancer cells. Pharmaceutical Biology, 54(7), 1223-1236.
Lee, E. L., & Westcarth, L. (2012). Neurotoxicity associated with cancer therapy. Journal of Advanced Practitioner in Oncology, 3(1), 11-21.
Leigh, M.J. (2003). Health benefits of grape seed proanthocyanidin extract (GSPE). Nutrition Noteworthy, 6(1), article 5.
Li, F., Zhou, X., Zhou, H., Jia, J., Li, L., Zhai, S., & Yan, B.(2016).ReducingbothPgpoverexpressionanddrug efflux with anti-cancer gold-paclitaxel nanoconjugates. PLoS One, 11(7), 1-16.
Poddar, S., Sultanal, R., Sultana, R., Mohammad, M., Azad, M. A. K., & Hasnat, A. (2009). Pattern of adverse drug reactions due to cancer chemotherapy in tertiary care teaching hospital in Bangladesh. Dhaka University Journal of Pharmaceutical Sciences, 8(1), 11-16.
Ramadori, G., & Cameron, S. (2010). Effects of systemic chemotherapy on the liver. Annals of Hepatology, 9(2), 133-143.
Sari, L.M., Subita, G.P., El Auerkari. (2017). Potential antioxidant and cytotoxic activities of areca nut (Areca catechu Linn.) extract in human oral squamous cell carcinoma and keratinocyte cells. Asian Journal of Pharmaceutical and Clinical Research, 10 (10), 286- 291.
Setiawati A., Susidarti R.A., & Meiyanto, E. (2011). The increase of cytotoxic effects of doxorubicin by hesperidin to the T47D cell. Bionatura - Jurnal Ilmu – Ilmu Hayati dan Fisik, 13(2), 85-92.
Smeltzer & Bare. (2002). Keperawatan Medikal Bedah. Ed. 8 Vol. 1, Jakarta: EGC.
The Jakarta Breast Cancer Foundation Dharmais Hospital. (2009). Retrieved from
Fitrianingsih, Fitrianingsih; Maharini, Indri; and Utami, Diah Tri
"Development of Ethanolic Extract of Pinang Masak Jambi (Areca Catechu L.) as A Modulator of Doxorubicin Cytotoxic Effect in Breast Cancer Therapy,"
Pharmaceutical Sciences and Research: Vol. 7
, Article 6.
Available at: https://scholarhub.ui.ac.id/psr/vol7/iss1/6