Summary
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 μg/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.
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Abbreviations
- PTX:
-
pentoxifylline
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Dedicated to Professor Dr. med. D. Schmähl on the occasion of his 65th birthday
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Petru, E., Boike, G. & Sevin, B.U. Potentiation of cisplatin cytotoxicity by methylxanthines in vitro. J Cancer Res Clin Oncol 116, 431–433 (1990). https://doi.org/10.1007/BF01612988
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DOI: https://doi.org/10.1007/BF01612988