Abstract 3979: In vitro modeling of pharmacodynamics of resveratrol-induced anti-proliferation in breast cancer cells

Abstract

Abstract We and others have shown that resveratrol, a naturally-occurring stilbene, induces p53-dependent apoptosis in human and animal cancer cell lines. The molecular basis of induction of apoptosis by resveratrol includes activation and nuclear translocation of mitogen-activated protein kinase (MAPK; ERK1/2) and MAPK-mediated Ser-15 phosphorylation of p53 (pSer15-p53). In this study, we used a newly developing perfusion bellows cell culture system to investigate resveratrol-induced apoptosis in the human estrogen receptor (ER)-negative breast cancer MDA-MB-231 cells. The cell culture system is a disposable bioreactor capable of high density cell culture for studies of anti-cancer drugs. Bellows-induced alternate flow of culture medium and air through porous matrices where cells are grown provides a relatively low shear, high aeration, foam-free culture environment. Medium level is raised and lowered to submerge and expose matrices to create a dynamic interface between air and media on the cell surface. Anchorage-dependent cells are grown on plastic flakes in the system; the flakes facilitate harvesting of whole cells for analysis. After 6 days incubation, the IC50 of resveratrol-induced apoptosis was 0.1 μM. Short term incubation with 10 μM resveratrol for 6 days inhibited cell proliferation by 75%. Using an injection system to pump media with different concentrations of resveratrol (0.5 μM to 100 μM), we were able to reproduce the resveratrol-induced anti-proliferation effect in the perfusion bellows culture system. Incubating the cells in either acidic or alkaline condition did not affect anti-proliferation induced by resveratrol. The effect of resveratrol-induced apoptosis is based on increasing transcription of pro-apoptotic p53-dependent genes such as PIG3, c-fos, c-jun and BAD. The aim of the present study is to establish the pharmacodynamics of resveratrol in the suppression or elimination of human breast cancer cells. With the use of the perfusion bellows cell culture system we will provide an efficient, convenient and financially beneficial method for determining optimal regimens for the effective suppression and elimination of these cancer cells. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3979.