Abstract 1989: The effect of resveratrol combined with DFMO or DenSpm on MCF-7 breast cancer cells and MCF-10a non-cancerous cells

Resveratrol, (3,5,49-trihydroxy-trans-stilbene), was first reported to act as a chemo-preventative anticancer compound in mice by Jang et al. in 1997. Resveratrol has been shown to induce apoptosis and reduce both cell viability and mitotic index in many cancer cell lines, including MCF-7. The current work extends these studies to determine its effects on glucose utilization and enzymes involved in polyamine metabolism. Glucose uptake was found to be reduced in MCF-7 cells treated with resveratrol. Work in other labs has shown resveratrol to sensitize cancer cells to other chemotherapeutic compounds. In the present study, the effects of combinations of resveratrol with compounds that affect polyamine metabolism, DFMO (difluoromethylornithine) and DenSpm (N1, N11-diethylnorspermine), were tested. Both DFMO and DenSpm were found to reduce cell proliferation and mitotic index in MCF-7 cell lines and more importantly, a synergistic effect was observed when these compounds were used in combination with resveratrol. In this investigation resveratrol was also found to induce apoptosis and reduce cell viability, mitotic index, and glucose uptake in non-cancerous, transformed mammary epithelial cells (MCF-10a). Similar findings have been reported with other non-cancerous cells including intestinal smooth muscle cells (Garcia et al., 2011). The combination of resveratrol and DFMO also reduced glucose uptake, proliferation, and mitotic index in this non-cancerous cell line (MCF-10a). These compounds were found to affect the expression of ODC (ornithine decarboxylase) and SSAT (spermidine/spermine acetyl transferase), enzymes involved in polyamine metabolism, and other proteins involved in cell cycle regulation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1989. doi:1538-7445.AM2012-1989