Protective Role of Vanillic Acid against Diethylnitrosamine- and 1,2-Dimethylhydrazine-Induced Hepatocarcinogenesis in Rats.

Charatda Punvittayagul,Kanokwan Jarukamjorn,Rawiwan Wongpoomchai,Arpamas Chariyakornkul

doi:10.3390/molecules26092718

Charatda Punvittayagul, Kanokwan Jarukamjorn + Show 2 more

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https://doi.org/10.3390/molecules26092718

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Abstract

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.

Highlights

Today, the trend for food as an attractive source of therapeutic candidates for various diseases is increasing
Hepatic glutathione S-transferase placental form (GST-P) positive foci using immunohistochemistry and colonic aberrant crypt foci (ACF) using methylene blue staining were used as the end-point markers of carcinogenesis, as we have reported previously [14]
We found that treatment with vanillic acid (VA) at a concentration of 75 mg kg−1 body weight (BW) did not induce the formation of hepatic GST-P positive foci and colonic ACF

Summary

Introduction

The trend for food as an attractive source of therapeutic candidates for various diseases is increasing. Numerous reports have supported the use of foods as drugs in the prevention and treatment of diseases, including cancer. It is well-known that the mechanism of carcinogenesis involves multiple factors, such as oxidative stress, inflammation and tumor suppressor gene or oncogene mutations [1]. Curcumin and resveratrol were used in a clinical trial for colorectal cancer treatment [2]. Pre-clinical studies have demonstrated that tea polyphenol and soy isoflavone presented chemopreventive activity against prostate cancer [3]. Lycopene from tomatoes decreased both DNA damage and the tumor size of prostate cancer in human studies [4]. Many studies have reported the anti-cancer activity of various natural products, the search for more natural anticarcinogenic agents is still necessary

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