Phytochemicals such as polyphenols and flavonoids have been reported to regulate cellular signaling pathway in many cancer cells. Resveratrol and quercetin have been known to exert anti-inflammatory or anti-cancer effects through regulating several pathways. AMP-activated protein kinase (AMPK) is one of the most important protein kinases involved in signal pathways related to metabolic control. AMPK is regulated by AMP/ATP ratio and activated by ATP consumption. Recently, it has been reported that AMPK is involved in the regulation of proliferation and/or apoptosis in several cancer cells. Our study investigated the synergistic effects of resveratrol and quercetin on apoptosis and AMPK activation in MCF-7 breast cancer cells. Treatment with resveratrol and quercetin or co-treatment with resveratrol and quercetin for 24 h inhibited cancer cell proliferation, and increased apoptotic cell death. The synergistic effects of resveratrol and quercetin were observed both in the inhibition of cell growth and the acceleration of apoptotic cell death. Also, the combined treatment of resveratrol and quercetin more strongly activated AMPK, and this effect was abolished by AMPK inhibitor Compound C in MCF-7 breast cancer cells. Treatment of AICAR, synthetic AMPK activator also increased phospho-AMPK levels. Our results suggest that combined treatment of resveratrol and quercetin is a more effective way in controlling cancer proliferation and apoptosis. (Cancer Prev Res 14, 218-224, 2009)

Keywords: Resveratrol, Quercetin, MCF-7 breast cancer cells, Modulating AMP-activated protein kinase, Combination treatment