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Fluoxetine induces apoptosis in ovarian carcinoma cell line OVCAR-3 through reactive oxygen species-dependent activation of nuclear factor-kappaB.
Basic Clin Pharmacol Toxicol. 2010 Jun; 106(6):446-53.BC

Abstract

The apoptotic effect of fluoxetine (FLX), an antidepressant, against human epithelial ovarian cancer cell lines OVCAR-3 and SK-OV-3 was investigated in relation to the mitochondria-mediated cell death process and nuclear factor (NF)-kappaB activation. FLX-induced mitochondrial membrane permeability change and formation of reactive oxygen species, leading to cell death. FLX-induced increase in mitochondrial Bax levels, decrease in cytosolic Bid and Bcl-2 levels, loss of the mitochondrial transmembrane potential, cytochrome c release, caspase-3 activation and up-regulation of p53. Oxidant scavengers and Bay 11-7085 [an inhibitor of nuclear factor kappaB (NF-kappaB) activation] prevented the FLX-induced cell death, increase in phosphorylated inhibitory kappaB-alpha and NF-kappaB p65 levels, and binding of NF-kappaB p65 to DNA. Results from this study suggest that FLX may exhibit apoptotic effect against ovarian cancer cell lines by inducing the mitochondrial membrane permeability change, which leads to cytochrome c release and subsequent caspase-3 activation, through reactive oxygen species-dependent activation of NF-kappaB.

Authors+Show Affiliations

Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea. leecs@cau.ac.krNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20050848

Citation

Lee, Chung Soo, et al. "Fluoxetine Induces Apoptosis in Ovarian Carcinoma Cell Line OVCAR-3 Through Reactive Oxygen Species-dependent Activation of Nuclear Factor-kappaB." Basic & Clinical Pharmacology & Toxicology, vol. 106, no. 6, 2010, pp. 446-53.
Lee CS, Kim YJ, Jang ER, et al. Fluoxetine induces apoptosis in ovarian carcinoma cell line OVCAR-3 through reactive oxygen species-dependent activation of nuclear factor-kappaB. Basic Clin Pharmacol Toxicol. 2010;106(6):446-53.
Lee, C. S., Kim, Y. J., Jang, E. R., Kim, W., & Myung, S. C. (2010). Fluoxetine induces apoptosis in ovarian carcinoma cell line OVCAR-3 through reactive oxygen species-dependent activation of nuclear factor-kappaB. Basic & Clinical Pharmacology & Toxicology, 106(6), 446-53. https://doi.org/10.1111/j.1742-7843.2009.00509.x
Lee CS, et al. Fluoxetine Induces Apoptosis in Ovarian Carcinoma Cell Line OVCAR-3 Through Reactive Oxygen Species-dependent Activation of Nuclear Factor-kappaB. Basic Clin Pharmacol Toxicol. 2010;106(6):446-53. PubMed PMID: 20050848.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fluoxetine induces apoptosis in ovarian carcinoma cell line OVCAR-3 through reactive oxygen species-dependent activation of nuclear factor-kappaB. AU - Lee,Chung Soo, AU - Kim,Yun Jeong, AU - Jang,Eun Ra, AU - Kim,Wonyong, AU - Myung,Soon Chul, Y1 - 2009/12/29/ PY - 2010/1/7/entrez PY - 2010/1/7/pubmed PY - 2010/10/5/medline SP - 446 EP - 53 JF - Basic & clinical pharmacology & toxicology JO - Basic Clin. Pharmacol. Toxicol. VL - 106 IS - 6 N2 - The apoptotic effect of fluoxetine (FLX), an antidepressant, against human epithelial ovarian cancer cell lines OVCAR-3 and SK-OV-3 was investigated in relation to the mitochondria-mediated cell death process and nuclear factor (NF)-kappaB activation. FLX-induced mitochondrial membrane permeability change and formation of reactive oxygen species, leading to cell death. FLX-induced increase in mitochondrial Bax levels, decrease in cytosolic Bid and Bcl-2 levels, loss of the mitochondrial transmembrane potential, cytochrome c release, caspase-3 activation and up-regulation of p53. Oxidant scavengers and Bay 11-7085 [an inhibitor of nuclear factor kappaB (NF-kappaB) activation] prevented the FLX-induced cell death, increase in phosphorylated inhibitory kappaB-alpha and NF-kappaB p65 levels, and binding of NF-kappaB p65 to DNA. Results from this study suggest that FLX may exhibit apoptotic effect against ovarian cancer cell lines by inducing the mitochondrial membrane permeability change, which leads to cytochrome c release and subsequent caspase-3 activation, through reactive oxygen species-dependent activation of NF-kappaB. SN - 1742-7843 UR - https://www.unboundmedicine.com/medline/citation/20050848/Fluoxetine_induces_apoptosis_in_ovarian_carcinoma_cell_line_OVCAR_3_through_reactive_oxygen_species_dependent_activation_of_nuclear_factor_kappaB_ L2 - https://doi.org/10.1111/j.1742-7843.2009.00509.x DB - PRIME DP - Unbound Medicine ER -