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Dietary Vitamin A Supplementation Decreases Colorectal Cancer Liver Metastases in Mice

Previously, we showed that retinol inhibited all‐trans‐retinoic acid (ATRA)‐resistant human colon cancer cell invasion via a retinoic acid receptor‐independent mechanism in vitro. The objective of the current study was to determine if dietary retinol inhibited the metastasis of ATRA‐resistant colon cancer cells in a nude mouse xenograft model. Ninety female nude mice (BALB/cAnNCr‐nu/nu) aged 6 to 8 weeks old were intrasplenically injected with 2 x 106 wild type HCT‐116 ATRA‐resistant human colon cancer cells. Purified AIN‐76 rodent diet was consumed pre‐injection. Immediately following injection the mice were randomly assigned to diets containing 2,400 (control), 12,000, 25,000, 50,000, 100,000 or 200,000 IU vitamin A/kg diet as retinyl palmitate. These diets provided 1, 5, 10, 20, 40 and 80X the daily vitamin A requirement of mice. The mice consumed these diets for five weeks prior to sacrifice. Livers and spleens were excised at the time of sacrifice and examined for the presence of primary tumors (spleen) or metastases (liver). Consumption of diets containing 50,000, 100,000, or 200,000 IU vitamin A/kg diet resulted in a decrease in tumor incidence to 72.6%, 72.6%, and 45.2%, respectively, of control. Thus, supplemental dietary vitamin A may be an effective chemotherapeutic agent to decrease the hepatic metastasis of colon cancer.