Metabolism of all-trans-retinol in normal human cell strains and squamous cell carcinoma (SCC) lines from the oral cavity and skin: reduced esterification of retinol in SCC lines.
Academic Article
Overview
abstract
Retinoids, metabolites and synthetic derivatives of vitamin A (retinol), have been shown to inhibit carcinogenesis in various epithelial tissues in animal model systems and to have clinical efficacy as chemotherapeutic agents against certain types of cancer, including squamous cell carcinomas (SCCs). We examined the metabolism of [3H]retinol in normal human cell strains and SCC lines from the oral cavity and skin, and we report here that the cultured normal human epithelial cell strains esterified [3H]retinol to a much greater extent than the SCC lines. Furthermore, microsomal extracts of normal cell strains (e.g., OKF4) exhibited about 7-fold more palmityl-CoA-dependent, phenylmethylsulfonyl fluoride-resistant retinol esterification activity than extracts from SCC lines (e.g., SCC25). The fact that the esteriflcation of retinol was phenylmethylsulfonyl fluoride resistant suggests that the enzyme acyl-CoA:retinol acyltransferase is involved. Culture of both the normal and SCC lines in the presence of 1 microM all-trans-retinoic acid (RA) for 48 h enhanced the formation of [3H]retinyl esters from [3H]retinol. All of the cell lines examined can also metabolize [3H]retinol to [3H]RA, [3H]14-hydroxy-4,14-retroretinol, [3H]retinaldehyde, and [3H]3,4-didehydroretinol, but this metabolism occurs to varying extents in different cell lines. Culture of the cells in the presence of RA for 48 h did not affect the subsequent metabolism of [3H]retinol to [3H]RA and [3H]14-hydroxy-4,14-retroretinol, but it did reduce the metabolism of [3H]retinol to [3H]3,4-didehydroretinol. When cultured for 6-10 h in the presence of nanomolar concentrations of exogenous [3H]retinol, both the normal and SCC lines had much higher intracellular [3H]retinol concentrations, in the micromolar range. No correlation was seen between CRABP II or CRBP I mRNA levels and the levels of either intracellular [3H]retinol or [3H]retinol metabolism in these lines. The reduced ability to esterify retinol in these tumor cells may result in inappropriate cell growth and the loss of normal differentiation responses because of the lack of a sufficient amount of internal retinol stored as retinyl esters.
