Inhibition of cell proliferation T47D BREAST CANCER BY COMBINATION doxorubicin, ethanolic extract of ginger rhizome (Curcuma xanthorrizaRoxb) AND LEAF EXTRACT ethanolic ficus septica (Ficus septica Burm.F.) MODULATION THROUGH CELL CYCLE

ABSTRACT: Breast Cancer is the cancer with the highest level of incidence both in Indonesia and in the world. Doxorubicin is the most proliferated chemotherapy agent for breast cancer therapy. Aside from the usage of single chemotherapy agent, co-chemotherapy which combine chemotherapy agent with another agent, is now being researched for clinical application. Co-chemotherapy effort is applied in order to reduce the side effect of chemotherapy and to increase the efficacy level of the doxorubicin. Furthermore, co-chemotherapy also conducted in order to hold the level of doxorubicin resistance of cancer cell which can make the therapy more efficient. Ethanolic Extract of Curcuma Rhizome (EEC) and Ethanolic Extract of Awar-Awar's Leaf (EEA) have been proved to have anticancer nature against many kinds of cancer cell. Therefore, further research needs to be done regarding the combination between EEA and EEC as a chemopreventive agent against breast cancer cell. This research is intended to test the combined activity between EEA and EEC and also its combination with doxorubicin as a chemotherapy agent. This research also test the ability of the combined activity in triggering the apoptosis process and modulating the cell cycle on breast cancer cell T47D. Single and combined cytotoxicity test are conducted using MTT assay. The apoptosis test and cell cycle profiling are done using flowcytometry. The combined usages of EEA and EEC in combination with doxorubicin are expected to enhance the level cytotoxicity by inducting apoptosis and modulating the cell cycle on cell T47D. EEA and EEC showed cytotoxic effect on cell T47D with level of IC50 on 6 mikrogram/ml and 30 mikrogram/ml. Meanwhile the value of IC50 in doxorubicin is 60 nM. Those three compounds are then combined with IC50 concentric at 1/6. The combination between EEA (1C50 mikrogram/ml), EEC (5 mikrogram/ml) and doxorubicin (10 nM) are able to lower the cell viability up to 55,70% and have a synergic effect with Combination Index (CI) value at 0,63. The combination of those three compounds resulted in accumulation of cell at the S phase (31,24%) and able to a few enhance the apoptosis. Those results proved tat EEA and EEC can be developed as a co-chemotherapy agent alongside with doxorubicin in order to improve the effectiveness of breast cancer therapy.