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

Wei-Ting Chen; Fei-Ting Hsu; Yu-Chang Liu; Cheng-Hsien Chen; Li-Cho Hsu; Song-Shei Lin

doi:10.3390/ijms20030757

International Journal of Molecular Sciences (Feb 2019)

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

Wei-Ting Chen,
Fei-Ting Hsu,
Yu-Chang Liu,
Cheng-Hsien Chen,
Li-Cho Hsu,
Song-Shei Lin

Affiliations

Wei-Ting Chen: Department of Medical Imaging and Radiological Sciences, Central Taiwan University of Science and Technology, Taichung 406, Taiwan
Fei-Ting Hsu: Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan
Yu-Chang Liu: Department of Medical Imaging and Radiological Sciences, Central Taiwan University of Science and Technology, Taichung 406, Taiwan
Cheng-Hsien Chen: Department of Surgery, Show Chwan Memorial Hospital, Changhua 500, Taiwan
Li-Cho Hsu: Division of Endocrinology and Metabolism, Department of Medicine, National Yang-Ming University Hospital, Yilan 260, Taiwan
Song-Shei Lin: Department of Medical Imaging and Radiological Sciences, Central Taiwan University of Science and Technology, Taichung 406, Taiwan

DOI: https://doi.org/10.3390/ijms20030757
Journal volume & issue: Vol. 20, no. 3
p. 757

Abstract

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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.

Published in International Journal of Molecular Sciences

ISSN: 1661-6596 (Print); 1422-0067 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General); Science: Chemistry
Website: http://www.mdpi.com/journal/ijms

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