Anti-carcinogenic effect of a new analogue 4′-chloroflavanone from flavanone in human breast cancer cells

Abstract

We investigated the antiproliferative effects of synthetic flavanone derivatives using an MTT assay in MCF-7 and MDA-MB-453 cells. When cells were treated with synthetic flavanone derivatives in concentrations ranging from 1 to 200 μM for 48 h, cell growth decreased at concentrations >50 μM. 4′-Chloroflavanone is more potent than flavanone among the synthetic flavanone derivatives. Exposure to 4′-chloroflavanone at 50 μM for 48 h caused cell cycle arrest in both MCF-7 and MDA-MB-453 cells. In addition, when 4′-chloroflavanone caused G1/S phase arrest, a decrease in CDK4 and cyclin D, together with an increase in p21Cip1, was observed in the cells. The p21Cip1 is a downstream target of p53 that may be affected by the activation of p53 by 4′-chloroflavanone. These results indicate that activation of p53 played some role in 4′-chloroflavanone-induced cell cycle arrest of human breast cancer cells. 4′-Chloroflavanone increased cytochrome c expression and decreased the expression of caspase-3, but did not change the expression of Bcl-2 and Bax. Activation of cytochrome c and its downstream target, caspase-3, is suggested to be an important inducer of the apoptosis process by 4′-chloroflavanone. 4′-Chloroflavanone inhibits cell proliferation through G1/S phase disruption and may induce apoptosis. Based on our findings, we propose that 4′-chloro-flavanone is useful as an anticancer drug.