Objectives Colon Cancer is the second deadliest cancerous disease worldwide among men and women. It has been estimated that more than half of colon cancers may be preventable by dietary intervention. A disturbance of the homeostasis between cellular proliferation and apoptosis is associated with colon cancer development. Watermelon (Citrullus lanatus) is rich in L-citrulline, a precursor of L-arginine. It has been shown that L-arginine may have anti-inflammatory roles and serves as a substrate for synthesis of nitric oxide, which in turn exerts wide-ranging physiological effects including tumoricidal effects via modification of cell kinetics. Our research examined if colon cancer can be prevented with the supplementation of watermelon powder by lowering cellular proliferation but enhancing apoptosis. Methods In order to test the hypothesis, 21-days old 32 Sprague Dawley rats were allocated to three groups; control, L- arginine (0.36% L-arginine) and watermelon powder (0.5%, w/w). Carcinogen azoxymethane was injected at week 4 and 5, and colon tissues were harvested at 5 week after the 2nd carcinogen injection. Cell proliferation and apoptosis were enumerated using a quantitative immunohistochemical analysis of Ki-67 antibody and TUNEL assay, respectively. Results Cell proliferation was mainly located bottom of colonic crypt (P < 0.05). Apoptotic cells were mostly located in the upper part of crypt (P < 0.05). L-arginine and watermelon fed rats lowered cell proliferation index and proliferative zone (P < 0.05). However, no difference was found on apoptosis among the three groups. Conclusions These results suggest that watermelon powder supplementation may reduce the risk of colon cancer by reducing cell proliferation rather than alteration of apoptosis. Further study will follow to determine the mechanism of anti-proliferative effect of watermelon supplementation. Funding Sources National Watermelon Promotion Board; SDSU/UCSD Cancer Center Partnership Scholars Program.
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).
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