Effect of curcumin on proliferation, cell cycle, and caspases and MCF-7 cells

We examined the mechanisms by which curcumin inhibits the growth of breast cancer cells. First, we investigated its antiproliferative effects on MCF-7 cells exposed to 2.5 to 40 μM curcumin for 24, 48 or 72 h. Curcumin inhibited cell proliferation in a dose-dependent and time-dependent manner (p<0.05) and resulted in significant cell cycle arrest in G1 phase after 72 h of treatment at concentrations of over 10 and 20 μM in MCF-7 cells, respectively (p<0.05). In addition, curcumin caused the accumulation of cells in sub-G0 phase in a dose-dependent manner in MCF-7 cells (p<0.05). As biomarkers of apoptosis induction, caspase-3 activity and caspase-9 activity were increased by curcumin in MCF-7 cells. To investigate the effects of curcumin on the proteins regulating cell cycle arrest, cells were treated with 20 μM curcumin for 72 h. Similar changes in the expression of regulatory proteins were detected in MCF-7 cells. Curcumin treatment resulted in decreases in cyclin D, cyclin E, CDK2, CDK4 and CDK6. The protein expression of CDK2 related to the G1 phase increased markedly with curcumin treatment. Curcumin treatment increased the expression of the CDK inhibitors p19INK4, p21Cip1 and p27Kip1. Thus, curcumin exerts its anticancer effects in human breast cancer cells via cell cycle arrest at the G1 phase.   Key words: Apoptosis, breast cancer, cell proliferation, cell cycle, caspase, curcumin.