Synergy BRAZILEIN cytotoxic effects of cisplatin THROUGH MODULATION AND CELL CYCLE AND APOPTOSIS INDUCTION OF BREAST CANCER CELLS T47D

ABSTRACT: Breast cancer is one of the most deadly cancer. The main priority of breast cancer treatment is the use of chemotherapeutic agents, especially cisplatin. However, cisplatin might also lead to diverse side-effects such as neurotoxicity, renaltoxicity, bone marrow suppression and cancer cell resistance. An approach recently develop to overcome side effect of cisplatin is to used of combined chemotherapeutic agent, i.e. brazilein. The focus of this study was to develop the potency of brazilein as chemotherapeutic agent by observing the cytotoxic effect, apoptosis induction and cell cycle modulation on T47D breast cancer cell line.The determination of cytotoxic activity of brazilein and cisplatin and the combination of them was evaluated using MTT assay to obtain the value of IC50 and CI (combnation index). The profile of cell cycle and apoptosis are observed using flowcytometry. Brazilein performed cytotoxic effect on T47D cells with IC50 of 28 μM. Combination brazilein ½ IC50 (14 μM) and cisplatin (8 μM) performed synergistic effect on T47D cell viability with CI value from o,405. The analysis on the cell cycle of the single treated cell againts brazilein showed accumulation in G1 phase, while the single treated on cisplatin showed accumulation in S phase. The combination of them showed accumulation on T47D cell cycle in G1 phase and increased apoptotic cells up to 36,23%. Combination of brazilein and cisplatin indicated synergy was related in apoptotic and cell cycle pathway. Thus, brazilein has potential to be developed as a cochemotherapeutic agent in combination with cisplatin.