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Homoharringtonine Exerts Anti-tumor Effects in Hepatocellular Carcinoma Through Activation of the Hippo Pathway

Hepatocellular carcinoma (HCC) is the most prevalent subtype of liver cancer with a mortality rate of approximately 3–6/100,000 and is the third leading cause of cancer-related death worldwide. Although several small-molecule drugs have been developed for the treatment of HCC, the choice of an agent...

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Autores principales: Wang, Haina, Wang, Rui, Huang, Dan, Li, Sihan, Gao, Beibei, Kang, Zhijie, Tang, Bo, Xie, Jiajun, Yan, Fanzhi, Liang, Rui, Li, Hua, Yan, Jinsong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943857/
https://www.ncbi.nlm.nih.gov/pubmed/33716735
http://dx.doi.org/10.3389/fphar.2021.592071
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author Wang, Haina
Wang, Rui
Huang, Dan
Li, Sihan
Gao, Beibei
Kang, Zhijie
Tang, Bo
Xie, Jiajun
Yan, Fanzhi
Liang, Rui
Li, Hua
Yan, Jinsong
author_facet Wang, Haina
Wang, Rui
Huang, Dan
Li, Sihan
Gao, Beibei
Kang, Zhijie
Tang, Bo
Xie, Jiajun
Yan, Fanzhi
Liang, Rui
Li, Hua
Yan, Jinsong
author_sort Wang, Haina
collection PubMed
description Hepatocellular carcinoma (HCC) is the most prevalent subtype of liver cancer with a mortality rate of approximately 3–6/100,000 and is the third leading cause of cancer-related death worldwide. Although several small-molecule drugs have been developed for the treatment of HCC, the choice of an agent for patients who require systemic chemotherapy at an advanced stage is still limited. The Hippo pathway is an evolutionarily conserved tumor suppressive pathway commonly dysregulated in HCC, which makes it a promising target for anti-HCC therapies. Homoharringtonine (HHT) is an FDA-approved anti-leukemia drug with proven strong anti-tumor activity in solid tumors. In this study, we found that HHT could significantly inhibit HCC cell growth by suppressing cell proliferation and colony formation. Moreover, HHT repressed cell invasion and migration remarkably. Additionally, HHT induced cell cycle arrest at S phase and promoted apoptosis. Most importantly, we showed that HHT-induced apoptosis was a consequence of the Hippo pathway activation. Consistently, the MST1/2 inhibitor, XMU-MP-1, could restore cell viability and reverse HHT-induced cell apoptosis. Furthermore, in vivo results confirmed the tumor inhibitory effect of HHT. Taken together, our findings suggest that HHT is a potential alternative therapeutic agent for the treatment of HCC.
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spelling pubmed-79438572021-03-11 Homoharringtonine Exerts Anti-tumor Effects in Hepatocellular Carcinoma Through Activation of the Hippo Pathway Wang, Haina Wang, Rui Huang, Dan Li, Sihan Gao, Beibei Kang, Zhijie Tang, Bo Xie, Jiajun Yan, Fanzhi Liang, Rui Li, Hua Yan, Jinsong Front Pharmacol Pharmacology Hepatocellular carcinoma (HCC) is the most prevalent subtype of liver cancer with a mortality rate of approximately 3–6/100,000 and is the third leading cause of cancer-related death worldwide. Although several small-molecule drugs have been developed for the treatment of HCC, the choice of an agent for patients who require systemic chemotherapy at an advanced stage is still limited. The Hippo pathway is an evolutionarily conserved tumor suppressive pathway commonly dysregulated in HCC, which makes it a promising target for anti-HCC therapies. Homoharringtonine (HHT) is an FDA-approved anti-leukemia drug with proven strong anti-tumor activity in solid tumors. In this study, we found that HHT could significantly inhibit HCC cell growth by suppressing cell proliferation and colony formation. Moreover, HHT repressed cell invasion and migration remarkably. Additionally, HHT induced cell cycle arrest at S phase and promoted apoptosis. Most importantly, we showed that HHT-induced apoptosis was a consequence of the Hippo pathway activation. Consistently, the MST1/2 inhibitor, XMU-MP-1, could restore cell viability and reverse HHT-induced cell apoptosis. Furthermore, in vivo results confirmed the tumor inhibitory effect of HHT. Taken together, our findings suggest that HHT is a potential alternative therapeutic agent for the treatment of HCC. Frontiers Media S.A. 2021-02-24 /pmc/articles/PMC7943857/ /pubmed/33716735 http://dx.doi.org/10.3389/fphar.2021.592071 Text en Copyright © 2021 Wang, Wang, Huang, Li, Gao, Kang, Tang, Xie, Yan, Liang, Li and Yan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Wang, Haina
Wang, Rui
Huang, Dan
Li, Sihan
Gao, Beibei
Kang, Zhijie
Tang, Bo
Xie, Jiajun
Yan, Fanzhi
Liang, Rui
Li, Hua
Yan, Jinsong
Homoharringtonine Exerts Anti-tumor Effects in Hepatocellular Carcinoma Through Activation of the Hippo Pathway
title Homoharringtonine Exerts Anti-tumor Effects in Hepatocellular Carcinoma Through Activation of the Hippo Pathway
title_full Homoharringtonine Exerts Anti-tumor Effects in Hepatocellular Carcinoma Through Activation of the Hippo Pathway
title_fullStr Homoharringtonine Exerts Anti-tumor Effects in Hepatocellular Carcinoma Through Activation of the Hippo Pathway
title_full_unstemmed Homoharringtonine Exerts Anti-tumor Effects in Hepatocellular Carcinoma Through Activation of the Hippo Pathway
title_short Homoharringtonine Exerts Anti-tumor Effects in Hepatocellular Carcinoma Through Activation of the Hippo Pathway
title_sort homoharringtonine exerts anti-tumor effects in hepatocellular carcinoma through activation of the hippo pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943857/
https://www.ncbi.nlm.nih.gov/pubmed/33716735
http://dx.doi.org/10.3389/fphar.2021.592071
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