Gastric cancer is the second leading cause of cancer death. It is well established that cigarette smoking increases the risk of gastric cancer. Most cases of gastric cancer are adenocarcinomas that occur in the mucosa or lining of the stomach. Carcinogens in smoke have a direct influence on the p53 tumor suppressor gene, which influences cell proliferation and cell apoptosis. A high level of p53 is a marker for genotoxic effects and tumorigenesis. Consumption of lycopene is linked to a decreased risk of gastric cancer. Other studies have shown that
lycopene can increase cell apoptosis of several cancers including prostate cancer, leukaemia and colon cancer. Epidemiological studies also indicate that the consumption tomatoes, which are high in lycopene, results in lower risk of gastric cancer. The molecular mechanism by which lycopene acts as anti-carcinogen is unknown.
The purpose of this study was to investigate the effect of lycopene on smoke exposure changes. The effect of lycopene supplementation on p53 protein levels, p53 target genes, cell growth and apoptosis in the gastric mucosa of ferrets were determined. The rats were divided in 2 main groups: ferrets that were exposed during 3 weeks to cigarette smoke and ferrest that were not. Each of the main groups were divided in 3 subgroups depending on lycopene supplementation: no lycopene, low dose and high dose of lycopene.
Ferrets not exposed to smoke showed elevated levels of lycopene in the gastric mucosa in a dose dependent manner. However, ferrets exposed to smoke had very low levels of lycopene in the gastric mucosa. Although the ferrets were give mostly trans isomers of lycopene, the main lycopene in the gastric mucosa was the cis isomers, suggesting that isomerization of lycopene occurred in the gastrointestinal tract.
The p53 and phosphorylated p53 protein levels were increased in ferrets exposed to cigarette smoke. This increase in levels was substantially lower in ferrets in the low and high dose lycopene group. Exposure to smoke also increased levels of cyclin D1 and proliferating nuclear antigen and decreased levels of p21, Bax-1 and cleaved caspase 3. Lycopene influence the changes in p21, Bax-1, cleaved caspase 3, cyclin D1 and proliferating nuclear antigen.
The study concluded that consumption of lycopene may reduce smoke induced changes and may protect against the development of gastric cancer.
Source: Chun Liu, Robert M. Russell, and Xiang-Dong Wang. Lycopene Supplementation Prevents Smoke-Induced Changes in p53, p53 Phosphorylation, Cell Proliferation and Apoptosis in the Gastric Mucosa of Ferrets. J. Nutr. 2006 136: 106-111