ON ACID synergistic effect Ursolic cytotoxic activity of doxorubicin IN BREAST CANCER CELLS MCF-7
ABSTRACT: Breast cancer is one of the most deadly cancers. The main priority of breast cancer treatment is the use of chemotheraupetic agents, especially doxorubicin. However, breast cancer treatment using doxorubicin has potency to generate cardiotoxicity and cancer cell resistance. An approach recently developed to overcome side effects of doxorubicin is to used of combined chemotheraupetic agent (cochemotherapeutic agent), i.e. ursolic acid. The aim of this research is to develop the potency of ursolic acid as cochemotherapeutic agent by observing the cytotoxic effect and cell cycle modulation on MCF-7 breast cancer cell lines. The determination of the cytotoxic activity of ursolic acid and doxorubicin and the combination of them was done using MTT assay to obtain the value of IC50 and CI (Combination Index). The profile of cell cycle is observed using flowcytometry and analyzed using Modfit LT 3.0 program. Ursolic acid had cytotoxic effect on MCF-7 breast cancer cell with IC50 of 37 μM. The combination ursolic acid ½ IC50 (19 μM) and doxorubicin ¼ IC50 (87,5 nM), 1/3 IC50 (116,7 nM), and ½ IC50 (175 nM); and combination ursolic acid 7/9 IC50 (28 μM) and doxorubicin with all of concentration performed synergistic effects on MCF-7 viability with CI value from 0,61 to 0,83. The analysis on the cycle of the single treated cell against ursolic acid showed accumulation in G1 phase, while the single treated on doxorubicin showed accumulation in G2 phase. The combination of ursolic acid and doxorubicin showed accumulation on MCF-7 cell cycle in G1 phase and induce apoptosis as well. Thus, ursolic acid has potential to be developed as a cochemotheraupetic agent in combination with doxorubicin.
