This study aimed to evaluate the
cancer chemopreventive activity of
vanillic acid (VA) in
diethylnitrosamine- and 1,2-dimethylhydrazine-induced liver and colon
carcinogenesis in rats. VA did not induce the formation of hepatic
glutathione S-transferase placental form (GST-P) positive foci and colonic
aberrant crypt foci, demonstrating no carcinogenic activity. VA (75 mg kg-1
body weight) could significantly reduce the number and areas of hepatic GST-P positive foci when administered before
carcinogen injections, but no such effect was seen when it was administered after
carcinogen injection. No protection was seen in the colon when VA was treated before or after
carcinogen injection. Immunohistochemical studies demonstrated the decreased expression of
proliferating cell nuclear antigen and the induction of apoptosis. Mechanistic studies showed that VA significantly induced the expression of GSTA-5 and Nrf-2 genes, which are associated with the detoxification system. Likewise, the antiproliferative effect was noticed by the reduction of
Cyclin D1 expression. The apoptotic activity may be due to the upregulation of
Caspase-3 and Bad levels and downregulation of the Bcl-2 level. These data suggest that VA exhibited significant protection against
diethylnitrosamine- and 1,2-dimethylhydrazine-induced hepatocarcinogenesis, which might be related to the induction of the detoxifying
enzyme, the reduction of proliferation and the induction of apoptosis.