Effect of topoisomerase modulators on cisplatin cytotoxicity in human ovarian carcinoma cells |
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| Affiliation: | 1. Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, 16 Medical Drive, 117600, Singapore;2. Department of Biology, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga L5L 1C6, Canada;3. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 2 Medical Drive, 117597, Singapore;4. NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 28 Medical Drive, 117456, Singapore;5. Immunology Program, Life Science Institute, National University of Singapore, 28 Medical Drive, 117456, Singapore;6. Singapore-HUJ Alliance for Research and Enterprise (SHARE), National University of Singapore, 1 CREATE Way, Innovation Wing, 138602, Singapore |
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| Abstract: | The in vitro interaction of modulators of topoisomerase I and II with cisplatin in human ovarian carcinoma cells might be synergistic. The interactions were evaluated by median effect analysis of survival data derived from continuous exposure to drug combinations for 10 days in colony-forming assays. The interaction between cisplatin and the topoisomerase I inhibitor camptothecin and the topoisomerase I activator β-lapachone was additive, as was that between cisplatin and the topoisomerase II inhibitor novobiocin. Despite the clinical efficacy of the combination of etoposide (a topoisomerase II inhibitor) and cisplatin, the combination index at 50% cell kill indicated antagonism between these two drugs. Thus, biochemical synergism at the cellular level is not a prerequisite of improved therapeutic efficacy. |
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