title: Acetaminophen enhances cisplatin- and paclitaxel-mediated cytotoxicity to SKOV3 human ovarian carcinoma.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Oregon Health and Sciences University, Portland, OR 97239, USA.
authors.forename: Ying-Jen Jeffrey
authors.initials: YJ
authors.lastname: Wu
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Neuwelt
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Muldoon
authors.forename: Edward A
authors.initials: EA
authors.lastname: Neuwelt
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011923:Rats, Nude; D017382:Reactive Oxygen Species; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; D000082:Acetaminophen; D005978:Glutathione; D017239:Paclitaxel; D002945:Cisplatin
keywords: Acetaminophen; SKOV3 cells; chemo-enhancement; cisplatin; glutathione; ovarian cancer