Modulatory Effect of Carnosic Acid on the Growth of ER-positive Human Breast Cancer Cells

Abstract

Epidemiological studies have indicated that the increased intakes of phenolic compounds are associated with the reduced risk of chronic diseases such as cancer of the breast, a leading cause of deaths among women. The objective of this study was to assess possible anti-cancer activity of phenolic compounds selected from the previous screening protocol. Sixteen polyphenols were evaluated for their MCF-7 cell cytotoxicity and inhibitory effect on TPA-induced PGE2 secretion. Carnosic acid was selected for further study, and its anti-proliferative, cell cycle arrest and apoptotic activities were measured. Results showed that hesperidin, cyanidin, delphinidin, pelargonidin, carnosic acid, myricetin and resveratrol significantly suppressed cell viability. PGE2 secretion was decreased by cyanidin, delphinidin, pelargonidin, picetannol, cinammic acid, carnosic acid and resveratrol. Carnosic acid at 20μM significantly suppressed cell proliferation. Carnosic acid treatment for 24 h significantly arrested cell cycle at G0/G1 phase and increased apoptotic cell number. The level of cyclinD1 protein was slightly decreased at 72 h, and no change was observed in cdk4 protein. Carnosic acid treatment slightly increased Bax protein, while it decreased Bcl-xL without statistical significances. Further studies on molecular mechanisms of anti-proliferative activity exerted by carnosic acid are required.