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Acacetin Inhibits Cell Proliferation and Induces Apoptosis in Human Hepatocellular Carcinoma Cell Lines

Human hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of death across the world. Recent evidence suggests that STAT3 regulates proliferative, survival, metastasis, and angiogenesis genes in HCC. Novel agents that suppress STAT3 activation can be used to pre...

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Autores principales: Alfwuaires, Manal, Elsawy, Hany, Sedky, Azza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9457933/
https://www.ncbi.nlm.nih.gov/pubmed/36080130
http://dx.doi.org/10.3390/molecules27175361
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author Alfwuaires, Manal
Elsawy, Hany
Sedky, Azza
author_facet Alfwuaires, Manal
Elsawy, Hany
Sedky, Azza
author_sort Alfwuaires, Manal
collection PubMed
description Human hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of death across the world. Recent evidence suggests that STAT3 regulates proliferative, survival, metastasis, and angiogenesis genes in HCC. Novel agents that suppress STAT3 activation can be used to prevent or treat HCC. We used a functional proteomics tumor pathway technology platform and multiple HCC cell lines to investigate the effects of acacetin (ACN) on STAT3 activation, protein kinases, phosphatases, products of STAT3-regulated genes, and apoptosis. ACN was found to inhibit STAT3 activation in a dose- and time-dependent manner in HCC cells. Upstream kinases c-Src, Janus-activated kinase 1, and Janus-activated kinase 2 were also inhibited. The ACN inhibition of STAT3 was abolished by vanadate treatment, suggesting the involvement of tyrosine phosphatase activity. ACN was found to suppress the protein expression of genes involved in proliferation, survival, and angiogenesis via STAT3 inhibition. ACN appears to be a novel STAT3 inhibitor and may be a promising therapeutic compound for application in the treatment of HCC and other cancers.
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spelling pubmed-94579332022-09-09 Acacetin Inhibits Cell Proliferation and Induces Apoptosis in Human Hepatocellular Carcinoma Cell Lines Alfwuaires, Manal Elsawy, Hany Sedky, Azza Molecules Article Human hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of death across the world. Recent evidence suggests that STAT3 regulates proliferative, survival, metastasis, and angiogenesis genes in HCC. Novel agents that suppress STAT3 activation can be used to prevent or treat HCC. We used a functional proteomics tumor pathway technology platform and multiple HCC cell lines to investigate the effects of acacetin (ACN) on STAT3 activation, protein kinases, phosphatases, products of STAT3-regulated genes, and apoptosis. ACN was found to inhibit STAT3 activation in a dose- and time-dependent manner in HCC cells. Upstream kinases c-Src, Janus-activated kinase 1, and Janus-activated kinase 2 were also inhibited. The ACN inhibition of STAT3 was abolished by vanadate treatment, suggesting the involvement of tyrosine phosphatase activity. ACN was found to suppress the protein expression of genes involved in proliferation, survival, and angiogenesis via STAT3 inhibition. ACN appears to be a novel STAT3 inhibitor and may be a promising therapeutic compound for application in the treatment of HCC and other cancers. MDPI 2022-08-23 /pmc/articles/PMC9457933/ /pubmed/36080130 http://dx.doi.org/10.3390/molecules27175361 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Alfwuaires, Manal
Elsawy, Hany
Sedky, Azza
Acacetin Inhibits Cell Proliferation and Induces Apoptosis in Human Hepatocellular Carcinoma Cell Lines
title Acacetin Inhibits Cell Proliferation and Induces Apoptosis in Human Hepatocellular Carcinoma Cell Lines
title_full Acacetin Inhibits Cell Proliferation and Induces Apoptosis in Human Hepatocellular Carcinoma Cell Lines
title_fullStr Acacetin Inhibits Cell Proliferation and Induces Apoptosis in Human Hepatocellular Carcinoma Cell Lines
title_full_unstemmed Acacetin Inhibits Cell Proliferation and Induces Apoptosis in Human Hepatocellular Carcinoma Cell Lines
title_short Acacetin Inhibits Cell Proliferation and Induces Apoptosis in Human Hepatocellular Carcinoma Cell Lines
title_sort acacetin inhibits cell proliferation and induces apoptosis in human hepatocellular carcinoma cell lines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9457933/
https://www.ncbi.nlm.nih.gov/pubmed/36080130
http://dx.doi.org/10.3390/molecules27175361
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