Stimulation of human monocyte oxidative burst and related cytotoxicity by tumor-promoting and non-tumor-promoting diterpene esters, indole alkaloids and polyacetate-type agents.
Human peripheral blood monocytes were cultured and exposed to plant diterpenes, indole alkaloids and polyacetates with various degrees of tumor-promoting activity. The effect of the above-mentioned encounter on monocyte function was examined, as expressed by H2O2 production and lysis of dog erythrocytes by the cells, and the inhibition of 3H-PDBu binding to the monocytes by the various test agents. The most effective reagents in both activation of monocyte function and inhibition of 3H-PDBu binding were 12-0-tetradecanoyl-phorbol 13-acetate (TPA), phorbol 12, 13 dibutyrate, teleocidin, and aplysiatoxin which are known to be strong tumor promoters. Strong stimulation of monocyte function was also exerted by the weak tumor promoters, phorbol 12-retinoate 13-acetate, mezerein and debromoaplysiatoxin. Non-tumor-promoting phorbol diterpenes such as phorbol 12, 13-diacetate, phorbol 12-myristate, phorbol 13-acetate and 4-alpha TPA were 1,000 times less effective than TPA in monocyte stimulation and inhibition of 3H-PDBu binding. These results indicate that stimulation of human monocyte H2O2 production and related cytotoxicity might discriminate effectively between tumor-promoting and non-tumor-promoting reagents.
D001667:Binding, Competitive; D029742:Caenorhabditis elegans Proteins; D002273:Carcinogens / Q000494:pharmacology*; D002352:Carrier Proteins; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008235:Lyngbya Toxins / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C; D011955:Receptors, Drug; D011971:Receptors, Immunologic / Q000378:metabolism; D013329:Structure-Activity Relationship
D029742:Caenorhabditis elegans Proteins; D002273:Carcinogens; D002352:Carrier Proteins; D004224:Diterpenes; D008235:Lyngbya Toxins; D010703:Phorbol Esters; D011955:Receptors, Drug; D011971:Receptors, Immunologic; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; C022176:teleocidins; C006610:aplysiatoxin; D006861:Hydrogen Peroxide; D011493:Protein Kinase C