Effect of Watermelon Powder Supplementation on Azoxymethane‐Induced Colon Carcinogenesis in Rats

Abstract

Colorectal cancer (CRC) is a public health concern and one of the most common cancers in men and women globally. Given the substantial morbidity and mortality associated with this disease, methods for prevention, in part through a diet high in fruits and vegetables, are under investigation. Specifically, watermelon may be a practical method for reducing CRC risk factors due to its high concentration of L‐citrulline, a precursor to L‐arginine, which plays a crucial role in endothelial nitric oxide (NO) production. Evidence suggests that increased levels of NO have tumoricidal effects; therefore, the purpose of this study was to determine the effects of watermelon powder supplementation on aberrant crypt foci (ACF) formation, precancerous lesions, and biomarkers that are associated with colon carcinogenesis in rats. Thirty‐two male Sprague‐Dawley rats, at 21 days old, were divided into three groups: control, 0.36% L‐arginine, or 0.5% watermelon powder. The 0.5% watermelon powder diet provided 0.36% of L‐arginine+L‐citrulline. Rats were injected subcutaneously with azoxymethane (dose of 15 mg/kg body weight), a carcinogenic agent, at the beginning of weeks 3 and 4. The watermelon group exhibited higher blood NO levels compared to the control group (P < 0.05). Both the L‐arginine and watermelon powder groups exhibited lower total numbers of ACF and high multiplicity aberrant crypt foci (HMACF, > 4 aberrant crypts/focus) (P < 0.01). The watermelon powder group exhibited lower 8‐hydroxyguanosine DNA damage in the blood (P < 0.05) compared to controls. Watermelon powder and L‐arginine downregulated 8‐oxoguanine DNA glycosylase (OGG1) gene expression (P < 0.05) and upregulated O6‐methylguanine DNA methyltransferase (MGMT) gene expression (P < 0.01). Cyclooxgenase‐2 (COX‐2) gene expression in the colon mucosa of the watermelon group was lower compared to the control group (P < 0.05). These results suggest that watermelon powder or L‐arginine consumption may reduce the risk of colon cancer by suppressing ACF formation through lowering oxidative DNA damage and inflammation, modulating DNA repair enzyme expression, and enhancing NO production.Support or Funding InformationThe study was funded by The US National Watermelon Promotion Board.