Imipramine-mediated Suppression of EGFR Signaling Attenuates Invasive and Progressive Abilities of Hepatocellular Carcinoma Cells

Chun-Yu Fu; Pen-An Liao; Tzu-Hsiang Lin; Fei-Ting Hsu; Dai-Cheng Dong; Wei-Ting Chen

doi:10.21873/anticanres.17360

Imipramine-mediated Suppression of EGFR Signaling Attenuates Invasive and Progressive Abilities of Hepatocellular Carcinoma Cells

Chun-Yu Fu, Pen-An Liao, Tzu-Hsiang Lin, Fei-Ting Hsu, Dai-Cheng Dong Wei-Ting Chen

Anticancer research, Vol.44(12), pp.5323-5335

01/12/2024

: https://doi.org/10.21873/anticanres.17360

: 39626916

: WOS:001380283100019

Apoptosis - drug effects

Carcinoma, Hepatocellular - drug therapy

Carcinoma, Hepatocellular - metabolism

Carcinoma, Hepatocellular - pathology

Cell Line, Tumor

Cell Movement - drug effects

Cell Proliferation - drug effects

ErbB Receptors - antagonists & inhibitors

ErbB Receptors - metabolism

Humans

Imipramine - pharmacology

Liver Neoplasms - drug therapy

Liver Neoplasms - metabolism

Liver Neoplasms - pathology

MAP Kinase Signaling System - drug effects

Neoplasm Invasiveness

Signal Transduction - drug effects

Hepatocellular carcinoma (HCC) is a primary liver cancer with high mortality rates worldwide, necessitating effective therapeutic strategies. Imipramine demonstrates the potential to augment standard treatments of different cancers, highlighting its therapeutic promise in oncology. This study aimed to investigate the potential regulation of imipramine on HCC. Cytotoxicity, apoptosis, metastasis, anti-apoptosis and signaling regulation were assessed in Huh7 and Hep3B cells using MTT assay, flow cytometry, and western blotting. Imipramine markedly induced cytotoxicity and Annexin-V activation in Huh7 and Hep3B cells in a time and dose-dependent manner. Mechanistically, imipramine induced cytotoxicity and apoptosis in HCC cells via both extrinsic (Fas-Fas-L) and intrinsic (mitochondrial) apoptosis pathways. It also suppressed HCC metastasis and inhibited epidermal growth factor receptor (EGFR)/mitogen-activated extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinases (ERKs) signaling. Imipramine shows promise in enhancing HCC treatment outcomes in patients and targets the EGFR/MEK/ERK signaling pathway in in vitro HCC models, thereby augmenting the effectiveness of standard therapies.

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esploro.research.conf.research.portal.label.prefix.inciteCollaboration: research.portal.fulldisplay.incitesHighlights.institutionCollaboration
esploro.research.conf.research.portal.label.prefix.inciteCitationTopics: 1 Clinical & Life Sciences; 1.25 Molecular & Cell Biology - Cancer, Autophagy & Apoptosis; 1.25.1247 NF-Kappa B
esploro.research.conf.research.portal.label.prefix.inciteWOSResearchAreas: Oncology
esploro.research.conf.research.portal.label.prefix.inciteESIResearchAreas: Clinical Medicine

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research.portal.fulldisplay.sdgs.source

: Imipramine-mediated Suppression of EGFR Signaling Attenuates Invasive and Progressive Abilities of Hepatocellular Carcinoma Cells
: Chun-Yu Fu (Author) - Chang Bing Show Chwan Memorial Hospital
Pen-An Liao (Author) - National Tsing Hua University, School of Medicine
Tzu-Hsiang Lin (Author) - Cathay General Hospital
Fei-Ting Hsu (Author) - Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C
Dai-Cheng Dong (Author) - China Medical University
Wei-Ting Chen (Author) - Central Taiwan University of Science and Technology
: Journal article
: 01/12/2024
: Anticancer research, Vol.44(12), pp.5323-5335
: English