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Int. J. Mol. Sci. 2019, 20(3), 757; https://doi.org/10.3390/ijms20030757

Fluoxetine Induces Apoptosis through Extrinsic/Intrinsic Pathways and Inhibits ERK/NF-κB-Modulated Anti-Apoptotic and Invasive Potential in Hepatocellular Carcinoma Cells In Vitro

1,2,3
,
4
,
1,5,6
,
7,†,* , 8,†,* and 1,†,*
1
Department of Medical Imaging and Radiological Sciences, Central Taiwan University of Science and Technology, Taichung 406, Taiwan
2
Department of Psychiatry, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung 813, Taiwan
3
Department of Physical Therapy, Shu-Zen Junior College of Medicine and Management, Kaohsiung 821, Taiwan
4
Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan
5
Department of Radiation Oncology, Chang Bing Show Chwan Memorial Hospital, Changhua 505, Taiwan
6
Department of Radiation Oncology, Show Chwan Memorial Hospital, Changhua 500, Taiwan
7
Department of Surgery, Show Chwan Memorial Hospital, Changhua 500, Taiwan
8
Division of Endocrinology and Metabolism, Department of Medicine, National Yang-Ming University Hospital, Yilan 260, Taiwan
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 25 November 2018 / Revised: 9 January 2019 / Accepted: 30 January 2019 / Published: 11 February 2019
(This article belongs to the Special Issue NF-κB and Cancer)
Full-Text   |   PDF [18189 KB, uploaded 11 February 2019]   |  

Abstract

The aim of the present study was to verify the effects of fluoxetine on dysregulation of apoptosis and invasive potential in human hepatocellular carcinoma (HCC) SK-Hep1 and Hep3B cells. Cells were treated with different concentrations of fluoxetine for different times. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assays were used for testing the effects of fluoxetine on cell viability. The regulation of apoptosis signaling, and anti-apoptotic, proliferation, and metastasis-associated proteins after fluoxetine treatment were assayed by flow cytometry and Western blotting assay. The detection of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation after fluoxetine treatment was performed by NF-κB reporter gene assay. The results demonstrated that fluoxetine significantly reduced cell viability, cell migration/invasion, NF-κB, extracellular signal-regulated kinases (ERK) activation, and expression of anti-apoptotic (Cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein (C-FLIP), Myeloid cell leukemia-1 (MCL-1), X-Linked inhibitor of apoptosis protein (XAIP), and Survivin), proliferation (Cyclin-D1), angiogenesis (vascular endothelial growth factor (VEGF)), and metastasis-associated proteins (matrix metalloproteinase-9 (MMP-9)). Fluoxetine also significantly induced apoptosis, unregulated extrinsic (activation of first apoptosis signal protein and ligand (Fas/FasL), and caspase-8) and intrinsic (loss of mitochondrial membrane potential (ΔΨm) pathways and increased Bcl-2 homologous antagonist killer (BAK) apoptosis signaling. Taken together, these results demonstrated that fluoxetine induced apoptosis through extrinsic/intrinsic pathways and diminished ERK/NF-κB-modulated anti-apoptotic and invasive potential in HCC cells in vitro. View Full-Text
Keywords: fluoxetine; human hepatocellular carcinoma; NF-κB; apoptosis fluoxetine; human hepatocellular carcinoma; NF-κB; apoptosis
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Chen, W.-T.; Hsu, F.-T.; Liu, Y.-C.; Chen, C.-H.; Hsu, L.-C.; Lin, S.-S. Fluoxetine Induces Apoptosis through Extrinsic/Intrinsic Pathways and Inhibits ERK/NF-κB-Modulated Anti-Apoptotic and Invasive Potential in Hepatocellular Carcinoma Cells In Vitro. Int. J. Mol. Sci. 2019, 20, 757.

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