Resveratrol enhances mitomycin C-mediated suppression of human colorectal cancer cell proliferation by up-regulation of p21WAF1/CIP1

Abstract

Background/aim: Studies have shown that natural products could potentially be employed in combination therapies to decrease toxicity to healthy tissues by chemotherapy drugs. No studies however, have investigated the potential modulatory role of resveratrol (RV) on mitomycin C (MMC)-mediated effects on colorectal cancer. The aim of the present study was to investigate the impact of RV on MMC-mediated inhibition of colorectal cancer cell proliferation and to assess the potential mechanisms for such effects.

Materials and methods: Primary cell lines generated from resected colorectal tumor specimens were treated with RV, MMC or RV+MMC and cell proliferation and gene expression analyses were performed.

Results: Suppression of cell proliferation by RV+MMC was significantly greater than individual treatments. RV+MMC synergistically modulated several genes but the up-regulation of p21(WAF1/CIP1) was several-fold greater.

Conclusion: The up-regulation of p21(WAF1/CIP1), which inhibits the cell cycle at G0/G1 and G2/M phases, may represent the predominant mechanism for enhancement of MMC-mediated anti-cancer effects by resveratrol.

Keywords: cell cycle; colorectal cancer; mitomycin C; p21WAF1/CIP1; resveratrol.