Effects of resveratrol in combination with 5-fluorouracil on N-methylnitrosourea-induced colon cancer in rats

Abstract

5-Fluorouracil (5-FU) is the most commonly used therapy and the conventional treatment for colorectal cancer. However, its toxicity to normal tissues is considered a major obstacle to successful cancer chemotherapy; thus, resveratrol is used in combination with 5-FU to reduce its toxicity. The goal of our study is to investigate the mechanisms underlying the effects of resveratrol alone and in combination with 5-FU in inhibiting experimentally induced colon cancer. Rats were divided into eight groups including control, resveratrol, 5-FU, resveratrol with 5FU, N-methylnitrosourea, treated group 1, 2, and 3 groups. Oxidant/antioxidant parameters, plasma NF-κB, and real-time PCR quantification of colonic P53 gene expression were assessed. Histopathological and immunohistochemistry of cyclooxygenases (COX-1, COX-2) were also performed. The data showed that N-methylnitrosourea significantly increased colon malondialdehyde (MDA), advanced oxidation protein products (AOPP), and nuclear factor-κB (NF-κB) concomitant with a reduction in superoxide dismutase (SOD) and a downregulation in P53 gene expression. Supplementation with resveratrol improved these values in treated groups. Thus, resveratrol is a highly promising antioxidant, anti-cancer, and anti-inflammatory compound through activating antioxidant defense system, its direct scavenging activity, as well as its biological activities through downregulation of COX-2 via suppression of NF-κB activation.