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

Ying Jen Jeffrey Wu, Alexander J. Neuwelt, Leslie Muldoon, Edward Neuwelt

Research output: Contribution to journalArticle

10 Citations (Scopus)

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. 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.

Original languageEnglish (US)
Pages (from-to)2391-2400
Number of pages10
JournalAnticancer Research
Volume33
Issue number6
StatePublished - Jun 2013

Fingerprint

Acetaminophen
Carcinoma
Glutathione
Ovarian Neoplasms
Neoplasms
Nude Rats
Mitochondrial Membrane Potential
Liver Neoplasms
Cisplatin
TP protocol
Reactive Oxygen Species
Apoptosis
Recurrence
Drug Therapy
Liver

Keywords

  • Acetaminophen
  • Chemo-enhancement
  • Cisplatin
  • Glutathione
  • Ovarian cancer
  • SKOV3 cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Acetaminophen enhances cisplatin- and paclitaxel-mediated cytotoxicity to SKOV3 human ovarian carcinoma. / Wu, Ying Jen Jeffrey; Neuwelt, Alexander J.; Muldoon, Leslie; Neuwelt, Edward.

In: Anticancer Research, Vol. 33, No. 6, 06.2013, p. 2391-2400.

Research output: Contribution to journalArticle

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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. 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.",
keywords = "Acetaminophen, Chemo-enhancement, Cisplatin, Glutathione, Ovarian cancer, SKOV3 cells",
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AU - Neuwelt, Alexander J.

AU - Muldoon, Leslie

AU - Neuwelt, Edward

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N2 - 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.

AB - 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.

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