Characterization of retinoic acid-induced alterations in the proliferation and differentiation of a murine and a human melanoma cell line in culture.

We employ the murine S91 and the human Hs939 melanoma cell lines for the characterization of various biochemical changes induced by retinoids. Retinoic acid (RA) causes a time-dependent, and reversible reduction in cell proliferation rate in liquid medium and inhibits growth in agar. The proportion of cells in the G1 phase of the cell cycle increases in RA-treated cells, and the uptake of TdR, UdR and Leu decreases. The growth inhibitory effect of RA is apparently not mediated via labilization of lysosomes, increase in cAMP or changes in the synthesis of prostaglandins or polyamines. Exposure to RA stimulates tyrosinase activity and increases melanin content severalfold over the levels found in untreated cells. Various retinoids exhibit the activities of RA; however, their potencies vary depending on their structure. Those possessing a free -COOH at C-15 are usually more effective than those with a different group or with a derivatized carboxyl. A positive correlation exists between the ability of retinoids with a free -COOH in C-15 to inhibit growth and to bind to an RA-binding protein found in the S91 melanoma cells. Future studies will explore recently discovered changes in the glycosylation of cell surface components and their relationship to the phenomena described here.