Acetaminophen enhances cisplatin- and paclitaxel-mediated cytotoxicity to SKOV3 human ovarian carcinoma

Background: Ovarian cancer is commonly treated with cisplatin/paclitaxel but many tumors become resistant. Acetaminophen reduced glutathione and enhanced chemotherapy efficacy in hepatic cancer treatment. The objective of this study was to examine if acetaminophen enhances the cytotoxicity of cisplatin/paclitaxel in ovarian cancer. Materials and Methods: SKOV3 human ovarian carcinoma cells in vitro and a subcutaneous tumor nude rat model were used and treated with cisplatin/paclitaxel with or without acetaminophen. Results: In vitro, acetaminophen enhanced apoptosis induced by cisplatin and paclitaxel with similar effects on glutathione, reactive oxygen species and mitochondrial membrane potential, but different effects on nuclear factor erythroid 2-related factor 2 (NRF2) translocation. In vivo, acetaminophen was uniformly distributed in tissues and significantly reduced hepatic glutathione. Acetaminophen enhanced the cisplatin chemotherapeutic effect by reducing tumor recurrence. Conclusion: Our results suggest that acetaminophen as a chemoenhancing adjuvant could improve the efficacy of cisplatin and paclitaxel in treating patients with ovarian carcinoma and other tumor types.