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Relationships among Retinoid Structure, Inhibition of Growth, and Cellular Retinoic Acid-binding Protein in Cultured S91 Melanoma Cells¹

Department of Developmental and Cell Biology, School of Biological Sciences, University of California, Irvine, California 92717

S91 melanoma cells, which are sensitive to retinoic acid and contain a cellular retinoic acid-binding protein (RABP), were used in an investigation of the possible correlation between the capacities of various retinoids to inhibit cell proliferation and to bind to the RABP. Each of 27 different retinoids was evaluated for growth-inhibitory activity by exposing S91 melanoma cells to various retinoid concentrations between 1 nM and 10 µM. Subsequently, the ability of 17 of these retinoids to compete with [³H]retinoic acid for binding to RABP was determined. The results demonstrate that in addition to retinoic acid, many retinoids are capable of inhibiting the proliferation of S91 melanoma cells, although some are considerably less active. A positive correlation was found between the abilities of retinoids possessing a free carboxyl group at carbon 15 to inhibit cell proliferation and to bind to RABP. The structure-activity relationships established with the S91 cells are compared with previous reports on the biological activities of various retinoids in other systems.

¹ Supported by USPHS Grant R01-CA-22823 from the National Cancer Institute. Presented in part at the 69th Annual Meeting of the American Association for Cancer Research (22).

² To whom requests for reprints should be addressed, at the Department of Biophysics, The Weizmann Institute of Science, Rehovot, Israel.

Received 10/ 1/79. Accepted 10/20/79.

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