Melanoma cell growth inhibition and melanocortin receptor downregulation induced by selective and non-selective retinoids

The purpose of this study was to investigate the effects of retinoid analogues with different retinoid receptor specifity on the growth of human D10 and Cloudman S91 mouse melanoma cells. We compared the growth inhibitory effects with the ability of retinoids to downregulate cell surface expression of the melanocortin receptor (MC1-R). Retinoic acid receptor (RAR)-gamma-selective retinoids exerted the most prominent growth effects, with up to 68% and 69% inhibition in D10 and S91 cells, respectively. A retinoid X receptor (RXR)-selective compound inhibited cell growth by only 14% and 23% in D10 and S91 cells, respectively. Growth inhibition by RAR alpha- and RAR beta-selective compounds was below 10% in both cells. In D10 cells, MC1-R downregulation was also induced most effectively by an RAR gamma-selective retinoid (84% relative to controls). RAR alpha-, RAR beta- and RXR-selective agonists induced only 16-24% MC1-R downregulation in these cells. The pattern for MC1-R downregulation was completely different in S91 cells. The RXR-selective compound was the most active (85%), followed by the RAR alpha-selective agonist (58%), the RAR gamma-selective compound (47%), and finally by the RAR beta-selective agonist (29%). We conclude that RAR gamma-selective retinoids may have potential as therapeutic agents in melanoma. Different selectivity profiles for growth inhibition and MC1-R downregulation in S91 cells suggest that these two retinoid effects are not directly dependent on each other. (C) 1998 Lippincott-Raven Publishers.