Potentiation of cisplatin cytotoxicity by methylxanthines in vitro.
The ability of two supposed DNA-repair inhibitors to modulate cisplatin-induced cytotoxicity in a human ovarian cancer cell line (CAOV-3) and a human cervical cancer cell line (Me-180) was investigated using a short-term chemosensitivity assay based on bioluminescence of cellular adenosine triphosphate (ATP). Cisplatin concentrations bracketing the reported peak plasma concentration (2.5 micrograms/ml) were used and the 50% inhibitory concentrations were determined by linear regression of log-transformed survival data. At 2.5 mM, the methylxanthine caffeine enhanced cisplatin sensitivity 2.9-fold in CAOV-3 cells and 2.7-fold in Me-180 cells. At 2.5 mM, pentoxifylline, a closely related methylxanthine, increased cisplatin sensitivity 2.9-fold in CAOV-3 cells and 3.4-fold in Me-180 cells. Chemical modification of cisplatin-induced cytotoxicity by assumed inhibition of DNA-repair mechanisms may hold promise for clinical application in the treatment of gynecological cancer.
Petru
E
E
Department of Obstetrics and Gynecology, University of Graz, Austria.
Boike
G
G
Sevin
B U
BU
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D002110:Caffeine / Q000494:pharmacology; D002470:Cell Survival / Q000502:physiology; D002945:Cisplatin / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D014970:Xanthines / Q000494:pharmacology*
D014970:Xanthines; C008514:methylxanthine; D002110:Caffeine; D000255:Adenosine Triphosphate; D002945:Cisplatin