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Parthenolide induces apoptosis by activating the mitochondrial and death receptor pathways and inhibits FAK-mediated cell invasion

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Abstract

The natural product parthenolide induces apoptosis in cancer cells. However, the mechanism of apoptosis in ovarian cancer cells exposed to parthenolide is not clear. In addition, it is unclear whether parthenolide-induced apoptosis is mediated by the formation of reactive oxygen species and the depletion of GSH contents, and the effect of parthenolide on the invasion and migration of human epithelial ovarian cancer cells has not been studied. Therefore, we investigated the effects of parthenolide exposure on apoptosis, cell adhesion, and migration using the human epithelial ovarian carcinoma cell lines OVCAR-3 and SK-OV-3. The results suggest that parthenolide 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 parthenolide appears to be mediated by the formation of reactive oxygen species and the depletion of GSH. Parthenolide inhibited fetal bovine serum-induced cell adhesion and migration of OVCAR-3 cells, possibly through the suppression the focal adhesion kinase-dependent activation of cytoskeletal-associated components. Therefore, parthenolide might be beneficial in the treatment of epithelial ovarian adenocarcinoma and combination therapy.

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Acknowledgments

This study was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A085138).

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Authors and Affiliations

  1. Department of Pathology, College of Medicine, Chung-Ang University, Seoul, 156-756, South Korea

    Sang Won Kwak & Eon Sub Park

  2. Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, 156-756, South Korea

    Chung Soo Lee

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  1. Sang Won Kwak
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Correspondence to Chung Soo Lee.

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Kwak, S.W., Park, E.S. & Lee, C.S. Parthenolide induces apoptosis by activating the mitochondrial and death receptor pathways and inhibits FAK-mediated cell invasion. Mol Cell Biochem 385, 133–144 (2014). https://doi.org/10.1007/s11010-013-1822-4

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  • DOI: https://doi.org/10.1007/s11010-013-1822-4

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