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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 387, Issue 9, pp 799–809 | Cite as

Menadione induces the formation of reactive oxygen species and depletion of GSH-mediated apoptosis and inhibits the FAK-mediated cell invasion

  • Yun Jeong Kim
  • Yong Kyoo Shin
  • Dong Suep Sohn
  • Chung Soo LeeEmail author
Original Article

Abstract

Menadione induces apoptosis in tumor cells. However, the mechanism of apoptosis in ovarian cancer cells exposed to menadione is not clear. In addition, it is unclear whether menadione-induced apoptosis is mediated by the depletion of glutathione (GSH) contents that is associated with the formation of reactive oxygen species. Furthermore, the effect of menadione on the invasion and migration of human epithelial ovarian cancer cells has not been studied. Therefore, we investigated the effects of menadione exposure on apoptosis, cell adhesion, and cell migration using the human epithelial ovarian carcinoma cell lines OVCAR-3 and SK-OV-3. The results suggest that menadione may induce apoptotic cell death in ovarian carcinoma cell lines by activating the mitochondrial pathway and the caspase-8- and Bid-dependent pathways. The apoptotic effect of menadione appears to be mediated by the formation of reactive oxygen species and the depletion of GSH. Menadione inhibited fetal-bovine-serum-induced cell adhesion and migration of OVCAR-3 cells, possibly through the suppression the focal adhesion kinase (FAK)-dependent activation of cytoskeletal-associated components. Therefore, menadione might be beneficial in the treatment of epithelial ovarian adenocarcinoma and combination therapy.

Keywords

Menadione Epithelial ovarian adenocarcinoma cell lines Apoptosis-related proteins Cell adhesion and migration 

Notes

Acknowledgments

This study was supported by grant of the BK21plus Skin Barrier Network Human Resources Development Team, National Research Foundation of Korea, Ministry of Education.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Yun Jeong Kim
    • 1
  • Yong Kyoo Shin
    • 1
  • Dong Suep Sohn
    • 2
  • Chung Soo Lee
    • 1
    Email author
  1. 1.Department of Pharmacology, College of Medicine, and the BK21plus Skin Barrier Network Human Resources Development TeamChung-Ang UniversitySeoulSouth Korea
  2. 2.Department of Thoracic and Cardiovascular SurgeryChung-Ang University HospitalSeoulSouth Korea

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