Effect of Watermelon Powder Supplementation on Colonic Aberrant Crypt Foci Formation

Abstract

Watermelon is a rich source of antioxidants and the amino acid L‐citrulline. L‐citrulline has been found to play a role in the treatment of various diseases such as pulmonary hypertension in infants and protected against kidney damage in type 1 diabetic mice. L‐citrulline is metabolized by the body into L‐arginine, which plays a role as a nitrogenous substrate responsible for the synthesis of nitric oxide (NO), an inorganic free radical gas at body temperature and modulator of vascular dilation. Various studies have investigated the effect of high NO levels as a cytotoxic substance towards cancer cells. Specifically, studies have examined NO in macrophage cytotoxicity. These studies state that cytokine activated rodent macrophages generate large concentrations of NO by the up‐regulation of expression of the inducible nitric oxide synthase gene (iNOS). Nitric oxide generated by this process is capable of killing different tumor cells; however, few studies have examined the role of watermelon and, consequently, L‐arginine on the progression of colon cancer. The purpose of this study was to determine the effect of watermelon powder consumption on the development of colon cancer by assessing aberrant crypt foci (ACF) formation, which are pre‐neoplastic lesions that are identifiable in the colon mucosa during the early progression of colon cancer. Thirty‐two male Sprague Dawley rats at 21 days old were administered either control, 0.36% L‐arginine, or 0.5% watermelon powder diets over a period of 9 weeks. The 0.5% watermelon powder diet provides 0.36% of L‐arginine+L‐citrulline. The rats were subcutaneously injected with azoxymethane, a carcinogenic agent, during weeks 3 and 4. Both L‐arginine and watermelon powder diets showed lower total number of ACF at 6.82 ± 0.75 and 4.73 ± 0.63 (mean ± standard error), respectively, compared to control group 26.50 ± 2.40 at P < 0.001. High multiplicity aberrant crypt foci (HMACF) (> 4 aberrant crypts/focus) were also lower in L‐arginine and watermelon powder diets at 1.09 ± 0.44 and 0.82 ± 0.23, respectively, than control group 8.10 ± 1.18 (P < 0.001). Lower total ACF and HMACF were also identified per centimeter of colon for L‐arginine and watermelon powder (P < 0.001). These results suggest that consumption of watermelon as a source for L‐arginine derived from L‐citrulline correspond with decreased ACF formation, which may reduce the risk of developing colon cancer.Support or Funding InformationThe study was funded by The US National Watermelon Promotion Board.