Hepatic Vitamin A Preloading Reduces Colorectal Cancer Metastatic Multiplicity in a Mouse Xenograft Model

Abstract

Previous research in our laboratory 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 vitamin A supplementation inhibited metastasis of ATRA-resistant colon cancer cells in a nude mouse xenograft model. Female nude mice (BALB/cAnNCr-nu/nu, n = 14 per group) consumed a control diet (2,400 IU retinyl palmitate/kg diet) or a vitamin A supplemented diet (200,000 IU retinyl palmitate/kg diet) for 1 mo prior to tumor cell injection to preload the liver with vitamin A. HCT-116, ATRA-resistant, human colon cancer cells were intrasplenically injected. Mice continued to consume their respective diets for 5 wk following surgery. Consumption of supplemental vitamin A decreased hepatic metastatic multiplicity to 17% of control. Hepatic and splenic retinol and retinyl ester concentrations were significantly higher in the mice supplemented with vitamin A when compared to mice consuming the control diet. Supplemental vitamin A did not decrease body weight, feed intake, or cause toxicity. Thus, supplemental dietary vitamin A may decrease the overall number of hepatic metastasis resulting from colon cancer.

ACKNOWLEDGMENTS

This research was supported by NIH grant #1R21CA120414-01A1 to Michelle A. Lane and NIEHS Center Grant ES 07784. The authors thank Erik Wilder, Kally O’Reilly, and Louis Doan for their assistance with the mouse surgery and Dr. Susan Fischer and Dr. Kaoru Kiguchi of the M.D. Anderson Cancer Center, University of Texas Smithville, Texas, for surgical training. We would also like to thank Dr. Claudio Conti, DVM, University of Texas M.D. Anderson Cancer Center, Smithville, Texas, for his pathological analyses of the liver sections.

Eun Young Park is currently at Samsung, Seoul, Korea.