Potentiation of anticancer agents by new synthetic isoprenoids. I. Inhibition of the growth of cultured mammalian cells.
In this study, 9 new synthetic isoprenoids with 9-10 isoprene chains were tested. One-fifth of the D10 value (concentration of drug that reduced colony-formation ability to 10% that of control) for each isoprenoid was calculated from dose-response curves of Chinese hamster V79 cells or human HeLa cells in culture. That dose was combined with various anticancer agent [1-(4-amino-2-methylpyrimidin-5-yl)methyl-3-(2-chloroethyl)-3-n itrosurea HCl, bleomycin A2 (BLM), cisplatin, doxorubicin (Dx), 5-fluorouracil, mitomycin, and 6-mercaptopurine] to test whether isoprenoids can potentiate the cytotoxic effect of anticancer agents against cultured mammalian cells. Among the 9 isoprenoids tested, decaprenoic acid, dacaprenylamine.HCl, and N-(p-methylbenzyl)decaprenylamine.HCl significantly potentiated BLM and Dx. Some isoprenoids increased intracellular levels of anticancer agents. Both enhanced uptake and reduced efflux of Dx were observed.
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004357:Drug Synergism; D006367:HeLa Cells / Q000187:drug effects; D007700:Kinetics; D008168:Lung; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000633:toxicity*; D014700:Verapamil / Q000494:pharmacology
D000970:Antineoplastic Agents; D013729:Terpenes; D014700:Verapamil