IMPROVEMENT IN EFFECT BRAZILEIN cytotoxic activity of doxorubicin ON CANCER CELLS INDUCED BY KOLON WiDr APOPTOSIS AND CELL CYCLE MODULATION
ABSTRACT: Colorectal cancer evidence is being the third most common cancer in world wide, but it is more common in developed countries. Nowadays, the medicinal treatment for colorectal cancer was using chemotherapy. Doxorubicin as the first line of chemotherapeutic agent for several type of cancer. But unfortunately, doxorubicin caused some side effect. So one of solution to overcome those problem is by using natural compound in combination with chemotherapy. Previous study showed that the use of combination chemotherapy can reduce side effects and increase the efficacy.The objection in this research is brazilein to combination chemotherapy. The previous study shows that brazilein could inhibit proliferation, induction of apoptotic and caused G1 arrest in MCF-7. Ethyl acetat extract and fraction of C. sappan caused cytotoxic effect in WiDr cells. So, brazilein estimated have caused cytotoxic activity in WiDr cells. Cytotoxic activity was evaluated by MTT assay and apoptosis analysis were performed by flow cytometry. Combination treatment was evaluated by using combination index (CI) method.Brazilein performed cytotoxic effect on WiDr cells, showing a decrease of cell viability in a concentration dependent manner, giving IC50 value of 130 μg/ml. Combination of brazilein and doxorubicin decreased cell viability up to 54.85% after 24 hour incubation. Evaluation by CI method showed that the combination of brazilein and doxorubicin indicated synergistic effect on WiDr cells in vitro. Further assay indicated that the combination caused cell cycle arrest in G2/M phase, but not increased apoptosis induction.These results provide evidence supporting the development of brazilein as doxorubicin co-chemotherapeutic agent, by enhancing its cytotoxic effect on colon cancer in vivo. Therefore, further study on its molecular mechanism needs to be conducted.
