Hepatic vitamin A preloading reduces colorectal cancer metastatic multiplicity in a mouse xenograft model.
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.
School of Family and Consumer Sciences, Nutrition and Foods Program, Texas State University-San Marcos, San Marcos, Texas 78666, USA.
Eun Young
EY
Park
Daniel
D
Pinali
Krista
K
Lindley
Michelle A
MA
Lane
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001711:Biotransformation; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D019587:Dietary Supplements; D004224:Diterpenes; D019008:Drug Resistance, Neoplasm; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D011897:Random Allocation; D000084562:Retinyl Esters; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution; D014212:Tretinoin / Q000494:pharmacology; D014801:Vitamin A / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D004224:Diterpenes; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate; D014212:Tretinoin