Anti-proliferative and gene expression actions of resveratrol in breast cancer cells in vitro.

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Chin YT, Hsieh MT, Yang SH, Tsai PW, Wang SH, Wang CC, Lee YS, Cheng GY, HuangFu WC, London D, Tang HY, Fu E, Yen Y, Liu LF, Lin HY, Davis PJ

Anti-proliferative and gene expression actions of resveratrol in breast cancer cells in vitro.

Oncotarget. 2014 Dec 30;5(24):12891-907.

PubMed ID

25436977 [ View in PubMed

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Abstract

We have used a perfusion bellows cell culture system to investigate resveratrolinduced anti-proliferation/apoptosis in a human estrogen receptor (ER)-negative breast cancer cell line (MDA-MB-231). Using an injection system to perfuse media with stilbene, we showed resveratrol (0.5 - 100 muM) to decrease cell proliferation in a concentration-dependent manner. Comparison of influx and medium efflux resveratrol concentrations revealed rapid disappearance of the stilbene, consistent with cell uptake and metabolism of the agent reported by others. Exposure of cells to 10 muM resveratrol for 4 h daily x 6 d inhibited cell proliferation by more than 60%. Variable extracellular acid-alkaline conditions (pH 6.8 - 8.6) affected basal cell proliferation rate, but did not alter anti-proliferation induced by resveratrol. Resveratrol-induced gene expression, including transcription of the most up-regulated genes and pro-apoptotic p53-dependent genes, was not affected by culture pH changes. The microarray findings in the context of induction of anti-proliferation with brief daily exposure of cells to resveratrol-and rapid disappearance of the compound in the perfusion system-are consistent with existence of an accessible initiation site for resveratrol actions on tumor cells, e.g., the cell surface receptor for resveratrol described on integrin alphavbeta3.