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Anticancer activity of paroxetine in human colon cancer cells: Involvement of MET and ERBB3

The concept of drug repositioning has recently received considerable attention in the field of oncology. In the present study, we propose that paroxetine can be used as a potent anticancer drug. Paroxetine, one of the selective serotonin reuptake inhibitors (SSRIs), has been widely prescribed for th...

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Autores principales: Jang, Won‐Jun, Jung, Sung Keun, Vo, Tam Thuy Lu, Jeong, Chul‐Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349215/
https://www.ncbi.nlm.nih.gov/pubmed/30421568
http://dx.doi.org/10.1111/jcmm.14011
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author Jang, Won‐Jun
Jung, Sung Keun
Vo, Tam Thuy Lu
Jeong, Chul‐Ho
author_facet Jang, Won‐Jun
Jung, Sung Keun
Vo, Tam Thuy Lu
Jeong, Chul‐Ho
author_sort Jang, Won‐Jun
collection PubMed
description The concept of drug repositioning has recently received considerable attention in the field of oncology. In the present study, we propose that paroxetine can be used as a potent anticancer drug. Paroxetine, one of the selective serotonin reuptake inhibitors (SSRIs), has been widely prescribed for the treatment of depression and anxiety disorders. Recently, SSRIs have been reported to have anticancer activity in various types of cancer cells; however, the underlying mechanisms of their action are not yet known. In this study, we investigated the potential anticancer effect of paroxetine in human colorectal cancer cells, HCT116 and HT‐29. Treatment with paroxetine reduced cell viability, which was associated with marked increase in apoptosis, in both the cell lines. Also, paroxetine effectively inhibited colony formation and 3D spheroid formation. We speculated that the mode of action of paroxetine might be through the inhibition of two major receptor tyrosine kinases – MET and ERBB3 – leading to the suppression of AKT, ERK and p38 activation and induction of JNK and caspase‐3 pathways. Moreover, in vivo experiments revealed that treatment of athymic nude mice bearing HT‐29 cells with paroxetine remarkably suppressed tumour growth. In conclusion, paroxetine is a potential therapeutic option for patients with colorectal cancer.
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spelling pubmed-63492152019-02-01 Anticancer activity of paroxetine in human colon cancer cells: Involvement of MET and ERBB3 Jang, Won‐Jun Jung, Sung Keun Vo, Tam Thuy Lu Jeong, Chul‐Ho J Cell Mol Med Original Articles The concept of drug repositioning has recently received considerable attention in the field of oncology. In the present study, we propose that paroxetine can be used as a potent anticancer drug. Paroxetine, one of the selective serotonin reuptake inhibitors (SSRIs), has been widely prescribed for the treatment of depression and anxiety disorders. Recently, SSRIs have been reported to have anticancer activity in various types of cancer cells; however, the underlying mechanisms of their action are not yet known. In this study, we investigated the potential anticancer effect of paroxetine in human colorectal cancer cells, HCT116 and HT‐29. Treatment with paroxetine reduced cell viability, which was associated with marked increase in apoptosis, in both the cell lines. Also, paroxetine effectively inhibited colony formation and 3D spheroid formation. We speculated that the mode of action of paroxetine might be through the inhibition of two major receptor tyrosine kinases – MET and ERBB3 – leading to the suppression of AKT, ERK and p38 activation and induction of JNK and caspase‐3 pathways. Moreover, in vivo experiments revealed that treatment of athymic nude mice bearing HT‐29 cells with paroxetine remarkably suppressed tumour growth. In conclusion, paroxetine is a potential therapeutic option for patients with colorectal cancer. John Wiley and Sons Inc. 2018-11-13 2019-02 /pmc/articles/PMC6349215/ /pubmed/30421568 http://dx.doi.org/10.1111/jcmm.14011 Text en © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Jang, Won‐Jun
Jung, Sung Keun
Vo, Tam Thuy Lu
Jeong, Chul‐Ho
Anticancer activity of paroxetine in human colon cancer cells: Involvement of MET and ERBB3
title Anticancer activity of paroxetine in human colon cancer cells: Involvement of MET and ERBB3
title_full Anticancer activity of paroxetine in human colon cancer cells: Involvement of MET and ERBB3
title_fullStr Anticancer activity of paroxetine in human colon cancer cells: Involvement of MET and ERBB3
title_full_unstemmed Anticancer activity of paroxetine in human colon cancer cells: Involvement of MET and ERBB3
title_short Anticancer activity of paroxetine in human colon cancer cells: Involvement of MET and ERBB3
title_sort anticancer activity of paroxetine in human colon cancer cells: involvement of met and erbb3
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349215/
https://www.ncbi.nlm.nih.gov/pubmed/30421568
http://dx.doi.org/10.1111/jcmm.14011
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