Hepatic vitamin A preloading reduces colorectal cancer metastatic multiplicity in a mouse xenograft model

Nutr Cancer. 2012;64(5):732-40. doi: 10.1080/01635581.2012.687425. Epub 2012 May 29.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Biotransformation
  • Carcinoma / drug therapy
  • Carcinoma / metabolism
  • Carcinoma / prevention & control*
  • Carcinoma / secondary
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Dietary Supplements*
  • Diterpenes
  • Drug Resistance, Neoplasm
  • Female
  • HCT116 Cells
  • Humans
  • Liver / metabolism*
  • Liver / pathology
  • Liver Neoplasms, Experimental / drug therapy
  • Liver Neoplasms, Experimental / metabolism
  • Liver Neoplasms, Experimental / prevention & control*
  • Liver Neoplasms, Experimental / secondary
  • Mice
  • Mice, Nude
  • Random Allocation
  • Spleen / metabolism
  • Spleen / pathology
  • Tissue Distribution
  • Tretinoin / pharmacology
  • Vitamin A / adverse effects
  • Vitamin A / analogs & derivatives*
  • Vitamin A / metabolism
  • Vitamin A / pharmacokinetics
  • Vitamin A / therapeutic use
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Diterpenes
  • Vitamin A
  • retinol palmitate
  • Tretinoin