Combination of Curcuma (Curcuma xanthorriza Roxb) and Awar-awar (Ficus septica Burm.F.) Ethanolic Extracts Enhance Doxorubicin to Modulate Cell Cycle Progression of T47D Cells

Laili Nailul Muna, Riris Istighfari Jenie


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.

Full Text:



Aggarwal, B.B., Shishodia, S., Sandur, S.K., Pandey, M.K. and Sethi, G., 2006, Inflammation and cancer: how hot is the link?, Biochem. Pharmacol., 72(11), 1605-1621. CrossRef

Damu, A.G., Kuo, P.C., Shi, L.S., Li, C.Y., Kuoh, C.S., Wu, P.L., et al., 2005, Phenanthroindolizidine alkaloids from the stems of Ficus septica, J. Nat. Prod., 68(7), 1071-1075. CrossRef

Foo, S.Y. and Nolan, G.P., 1999, NF-kappaB to the Rescue: RELs, Apoptosis and Cellular Transformation, Trends Genet., 15(6), 229-235. CrossRef

Haryanti, S., Pramono, S., Murwanti, R. and Meiyanto, E., 2016, The Synergistic Effect of Doxorubicin and Ethanolic Extracts of Caesalpinia sappan L. Wood and Ficus septica Burm. f. Leaves on Viability, Cell Cycle Progression, and Apoptosis Induction of MCF7 Cells, Indones. J. Biotechnol., 21(1) 29-37. CrossRef

Kang, J., Park, K., Chung, W., Hwang, J. and Lee, S., 2009, Xanthorrhizol, a natural sesquiterpenoid, induces apoptosis and growth arrest in HCT116 human colon cancer cells, J. Pharmacol. Sci., 111(3), 276-84. CrossRef

Kolb, R.H., Greer, P.M., Cao, P.T., Cowan, K.H. and Yan, Y., 2012, ERK1/2 signaling plays an important role in topoisomerase II poison-induced G2/M checkpoint activation, PLoS One, 7(11), e50281. CrossRef

Mechetner, E., Kyshtoobayeva, A., Zonis, S., Kim, H., Stroup, R., Garcia, R., et al., 1998, Levels of Multidrug Resistance (MDR1) P-Glycoprotein Expression by Human Breast Cancer Correlate with in vitro Resistance to Taxol and Doxorubicin, Clin. Cancer Res., 4(2), 389-398. Link

Nugroho, A.E., Hermawan, A., Putri, D.D., Novika, A. Meiyanto, E. and Kawaichi, M., 2013, Combinational effects of hexane insoluble fraction of Ficus septica Burm. F. and doxorubicin chemotherapy on T47D breast cancer cells, Asian Pac. J. Trop. Biomed., 3(4), 297-302. CrossRef

Sekti, D.A., Mubarok, M.F., Armandani, I., Junedy, S. and Meiyanto, E., 2010, Ekstrak Etanolik Daun Awar–awar (Ficus septica Burm. f.) Memacu Apoptosis Sel Kanker Payudara MCF-7 Melalui Penekanan Ekspresi Bcl-2, Maj. Obat Tradis., 15(3), 100–104. Link

Shah, M.A. and Schwartz, G.K., 2001, Cell cycle-mediated drug resistance: an emerging concept in cancer therapy, Clin. Cancer Res., 7(8), 2168-2181. Link

Sharma, G., Tyagi, A., Singh, R., Chan, D. and Agarwal, R., 2004, Synergistic anti-cancer effects of grape seed extract and conventional cytotoxic agent doxorubicin against human breast carcinoma cells, Breast Cancer Res. Treat., 85(1), 1–12. CrossRef

Su, C.C., Geng Lin, J. and Wei Chen, G., 2006, Down-regulation of Cdc25c, CDK1 and Cyclin B1 and Up-regulation of Wee1 by Curcumin Promotes Human Colon Cancer Colo 205 Cell Entry into G2/M-phase of Cell Cycle, Cancer Genom. Proteom., 3(1), 55-61. Link

Ueda, J.Y., Tezuka, Y., Banskota, A.H., Le Tran, Q., Tran, Q.K., Harimaya, Y., et al., 2002, Antiproliferative activity of Vietnamese medicinal plants, Biol. Pharm. Bull., 25(6), 753-760. CrossRef

Wattanapitayaku, S.K., Chularojmontri, L., Herunsalee, A., Charuchongkolwongse, S., Niumsakul, S. and Bauer, J.A., 2004, Screening of Antioxidants from Medicinal Plants for Cardioprotective Effect against Doxorubicin Toxicity, Basic Clin. Pharmacol. Toxicol., 96(1), 80-87. CrossRef

Widowati, W., Mozef, T., Risdian, C., Ratnawati, H., Tjahjani, S. and Sandra, F., 2011, The Comparison of Antioxidative and Proliferation Inhibitor Properties of Piper betle L., Catharanthus roseus [L] G.Don, Dendrophtoe petandra L., Curcuma mangga Val. Extracts on T47D Cancer Cell Line, Int. Res. J. Biochem. Bioinform., 1(2), 22-28. Link


Copyright (c) 2018 Laili Nailul Muna, Riris Istighfari Jenie

Indexed by:




Indonesian Society for Cancer Chemoprevention