Watermelon Powder Supplementation Reduces Colonic Cell Proliferation by Upregulating p21Waf1/Cip1 Expression

Abstract

Objectives Watermelon is high in L-citrulline, a precursor for L-arginine, which in turn may reduce the risk of colorectal cancer (CRC). Research has shown that L-arginine inhibits the hyperproliferation of colorectal tumor cells as a marker for CRC. The objective of this study was, therefore, to examine the effects of watermelon powder supplementation on colonic cell proliferation and their gene expression. The hypothesis was that watermelon powder supplementation would reduce CRC risk by regulating colonic expression of genes related to epithelial cell proliferation. Methods Thirty-two 21-day-old, male, Sprague Dawley rats were randomly assigned to one of the following isocaloric diets: 0.5% watermelon powder, 0.36% L-arginine, and control for 9 weeks. All animals were injected with azoxymethane (15 mg/kg body weight). Colonic cell proliferation was measured using ki-67 immunohistochemistry, and colonic gene expression was determined using a quantitative real-time polymerase chain reaction (PCR). Results Both watermelon powder and L-arginine groups exhibited lower proliferating index (P = 0.041) and lower proliferative zone (P = 0.041). In addition, watermelon powder and L-arginine supplementation upregulated p21Waf1/Cip1 gene expression (P = 0.048). There were no significant differences in the expression of Cyclin D1, Cyclin-dependent kinase 2 (CDK2), Cyclin-dependent kinase 4 (CDK4), and Peroxisome proliferator-activated receptor γ (PPARγ). Conclusions These results suggest that watermelon or L-arginine supplementation may decrease the risk of CRC as they both reduced proliferation by upregulating a cyclin-dependent kinase inhibitor. Additional markers for gene expression involving cell proliferation are needed to confirm the present findings. Funding Sources National Watermelon Promotion Board (NWPB 15–16) National Cancer Institutes of Health (U54CA132384 for SDSU and U54132379 for UCSD).