Alpha tocopheryl succinate inhibits melanocyte-stimulating hormone (MSH)-sensitive adenylate cyclase activity in melanoma cells.
D-alpha tocopheryl succinate (vitamin E succinate), which is known to induce differentiation and growth inhibition in murine B-16 melanoma cells, reduced basal and melanocyte-stimulating hormone (MSH)-stimulated adenylate cyclase (AC) activity in vitro. Vitamin E succinate treatment also reduced sodium fluoride- and forskoline-stimulated AC activity of melanoma cells in vitro. Treatment of cells with vitamin E succinate (6 micrograms/ml] for a period of 24 hours was sufficient to reduce MSH-stimulated AC activity. Other forms of vitamin E, such as d1-alpha tocopheryl nicotinate, d1-alpha tocopheryl acetate, and d1-alpha tocopherol, which did not affect growth or morphology of melanoma cells, were relatively less effective in altering basal and MSH-stimulated AC activity. Retinoic acid, which inhibited the growth of B-16 melanoma cells, also reduced basal and MSH-, NaF-, and forskolin-stimulated AC activity in vitro. Prostaglandin A2, which inhibited growth and altered morphology, did not change basal or MSH-stimulated AC activity. These results show that one of the mechanisms of action of vitamin E succinate and retinoic acid on melanoma cells may involve reduction of basal and MSH-sensitive AC activity, and this vitamin effect is not necessarily related to growth inhibition.
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Deparment of Radiology, School of Medicine, University of Colorado Health Sciences Center, Denver 80262.
Edwards-Prasad
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Prasad
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D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology*; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology; D011454:Prostaglandins A / Q000494:pharmacology; D012969:Sodium Fluoride / Q000494:pharmacology; D024505:Tocopherols; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D011454:Prostaglandins A; D014810:Vitamin E; D005576:Colforsin; D014212:Tretinoin; D012969:Sodium Fluoride; D009074:Melanocyte-Stimulating Hormones; D000262:Adenylyl Cyclases; C100008:prostaglandin A2; D024505:Tocopherols