Uptake of chylomicron remnant retinyl ester via the low density lipoprotein receptor: implications for the role of vitamin A as a possible preventive for some forms of cancer

Abstract

The anti-cancer action of retinoids (vitamin A and its metabolites) has been most successfully demonstrated in cell culture systems. In most of these investigations retinoic acid was found to be the most active retinoid [l-21. In such studies, however, the fat-soluble retinoic acid is dissolved in an organic solvent before it is added to the cells. Therefore, these in vitro systems do not take into account transport to and uptake by the target cells that must occur in vivo. The body has a specific and high-capacity transport system for retinol (bound to retinol-binding protein) and retinyl esters (bound to lipoproteins), but not for retinoic acid and its synthetic analogues [3]. Recent studies have shed some light on the in vivo transport of retinoids to cancer cells. Promising results have been obtained from an initial clinical trial in which children with acute myeloid leukaemia in remission were treated with high doses of retinol [4]. This treatment produces a significant increase in the plasma concentration of chylomicron remnant retinyl esters. Furthermore, in vitro studies have shown that physiological concentrations of retinyl palmitate bound to chylomicron remnants effectively induce differentiation and inhibit proliferation of human myeloid leukaemic cells in culture [S]. Thus the anti-cancer effect of vitamin A may be mediated via retinyl ester bound to chylomicron remnants, rather than by retinol bound to retinol-binding protein or free retinoic acid. The role of vitamin A as a possible preventive for various forms of cancer should be re-examined in the light of these findings.