Second stage tumor promoters: differences in biological potency and phorbol ester receptor affinity in C6 cells.
We have shown that the second stage tumor promoters mezerein (MEZ) and phorbol 12-retinoate 13-acetate (PRA) inhibit the gluccocorticoid-induced increase in glycerol phosphate dehydrogenase (GPDH) activity in C6 rat glioma cells with ED 50-values of 3.9 and 2.9 nM, respectively. Phorbol 12-myristate 13-acetate (PMA) was 10-fold less potent. MEZ was likewise more potent than PMA for inhibition of cAMP formation in response to isoproterenol. Binding competition studies using [3H]phorbol 12,13-dibutyrate ([3H]PDBu) yielded apparent Ki-values for MEZ and PRA of 50-70 nM. The large difference between the biological potencies of MEZ and PRA and their affinity for the major phorbol ester receptor suggest they may be acting through a more complicated mechanism in these cells.
D000818:Animals; D029742:Caenorhabditis elegans Proteins; D002273:Carcinogens; D002352:Carrier Proteins; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D004224:Diterpenes; D005910:Glioma / Q000378:metabolism; D005993:Glycerolphosphate Dehydrogenase / Q000037:antagonists & inhibitors; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000378:metabolism / Q000494:pharmacology*; D011493:Protein Kinase C; D051381:Rats; D011955:Receptors, Drug; D011971:Receptors, Immunologic / Q000378:metabolism*; D013729:Terpenes / Q000378:metabolism / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism / Q000494:pharmacology
D029742:Caenorhabditis elegans Proteins; D002273:Carcinogens; D002352:Carrier Proteins; D004224:Diterpenes; D010703:Phorbol Esters; D011955:Receptors, Drug; D011971:Receptors, Immunologic; D013729:Terpenes; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; C011309:mezerein; D015240:Phorbol 12,13-Dibutyrate; C032974:12-O-retinoylphorbol-13-acetate; D000242:Cyclic AMP; D005993:Glycerolphosphate Dehydrogenase; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate