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Galangin Inhibits Gastric Cancer Growth Through Enhancing STAT3 Mediated ROS Production

Galangin, a flavonoid isolated from the rhizome of Alpinia officinarum (Hance), exerts anticancer activities against many cancer cells such as liver cancer, breast cancer, lung cancer and esophageal cancer. However, the effect, as well as the underlying molecular mechanism of galangin on gastric can...

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Autores principales: Liang, Xiaohui, Wang, Ping, Yang, Chun, Huang, Fei, Wu, Hui, Shi, Hailian, Wu, Xiaojun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109028/
https://www.ncbi.nlm.nih.gov/pubmed/33981228
http://dx.doi.org/10.3389/fphar.2021.646628
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author Liang, Xiaohui
Wang, Ping
Yang, Chun
Huang, Fei
Wu, Hui
Shi, Hailian
Wu, Xiaojun
author_facet Liang, Xiaohui
Wang, Ping
Yang, Chun
Huang, Fei
Wu, Hui
Shi, Hailian
Wu, Xiaojun
author_sort Liang, Xiaohui
collection PubMed
description Galangin, a flavonoid isolated from the rhizome of Alpinia officinarum (Hance), exerts anticancer activities against many cancer cells such as liver cancer, breast cancer, lung cancer and esophageal cancer. However, the effect, as well as the underlying molecular mechanism of galangin on gastric cancer remains to be elucidated. In the present study, galangin inhibited cell viability of MGC 803 cells but not normal gastric mucosal epithelial GES-1 cells. It suppressed cell proliferation accompanied by reduced Ki67 and PCNA expression, promoted apoptosis shown by decreased Bcl-2 and elevated cleaved caspase-3 and cleaved PARP. And, galangin significantly inactivated JAK2/STAT3 pathway. When STAT3 was overexpressed, the proliferation inhibition and apoptosis promotion induced by galangin were abrogated. Meanwhile, galangin increased ROS accumulation, and reduced Nrf2 and NQO-1, but elevated HO-1 in MGC 803 cells. NAC, a ROS scavenger, rescued ROS over-accumulation and proliferation inhibition of galangin. STAT3 overexpression also counteracted excessive ROS accumulation induced by galangin. Consistent with the in vitro experiments, in nude mice exnografted with MGC 803 cells, galangin inhibited tumor growth and reversed the abnormally expressed proteins, such as p-JAK2, p-STAT3, Bcl-2, cleaved caspase-3, cleaved PARP, and Ki67. Taken together, galangin was suggested to inhibit the growth of MGC 803 cells through inducing apoptosis and decreasing cell proliferation, which might be mediated by modulating STAT3/ROS axis. Our findings implicate a potential application of galangin for gastric cancer therapy possibly with low toxicity.
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spelling pubmed-81090282021-05-11 Galangin Inhibits Gastric Cancer Growth Through Enhancing STAT3 Mediated ROS Production Liang, Xiaohui Wang, Ping Yang, Chun Huang, Fei Wu, Hui Shi, Hailian Wu, Xiaojun Front Pharmacol Pharmacology Galangin, a flavonoid isolated from the rhizome of Alpinia officinarum (Hance), exerts anticancer activities against many cancer cells such as liver cancer, breast cancer, lung cancer and esophageal cancer. However, the effect, as well as the underlying molecular mechanism of galangin on gastric cancer remains to be elucidated. In the present study, galangin inhibited cell viability of MGC 803 cells but not normal gastric mucosal epithelial GES-1 cells. It suppressed cell proliferation accompanied by reduced Ki67 and PCNA expression, promoted apoptosis shown by decreased Bcl-2 and elevated cleaved caspase-3 and cleaved PARP. And, galangin significantly inactivated JAK2/STAT3 pathway. When STAT3 was overexpressed, the proliferation inhibition and apoptosis promotion induced by galangin were abrogated. Meanwhile, galangin increased ROS accumulation, and reduced Nrf2 and NQO-1, but elevated HO-1 in MGC 803 cells. NAC, a ROS scavenger, rescued ROS over-accumulation and proliferation inhibition of galangin. STAT3 overexpression also counteracted excessive ROS accumulation induced by galangin. Consistent with the in vitro experiments, in nude mice exnografted with MGC 803 cells, galangin inhibited tumor growth and reversed the abnormally expressed proteins, such as p-JAK2, p-STAT3, Bcl-2, cleaved caspase-3, cleaved PARP, and Ki67. Taken together, galangin was suggested to inhibit the growth of MGC 803 cells through inducing apoptosis and decreasing cell proliferation, which might be mediated by modulating STAT3/ROS axis. Our findings implicate a potential application of galangin for gastric cancer therapy possibly with low toxicity. Frontiers Media S.A. 2021-04-26 /pmc/articles/PMC8109028/ /pubmed/33981228 http://dx.doi.org/10.3389/fphar.2021.646628 Text en Copyright © 2021 Liang, Wang, Yang, Huang, Wu, Shi and Wu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). 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
Liang, Xiaohui
Wang, Ping
Yang, Chun
Huang, Fei
Wu, Hui
Shi, Hailian
Wu, Xiaojun
Galangin Inhibits Gastric Cancer Growth Through Enhancing STAT3 Mediated ROS Production
title Galangin Inhibits Gastric Cancer Growth Through Enhancing STAT3 Mediated ROS Production
title_full Galangin Inhibits Gastric Cancer Growth Through Enhancing STAT3 Mediated ROS Production
title_fullStr Galangin Inhibits Gastric Cancer Growth Through Enhancing STAT3 Mediated ROS Production
title_full_unstemmed Galangin Inhibits Gastric Cancer Growth Through Enhancing STAT3 Mediated ROS Production
title_short Galangin Inhibits Gastric Cancer Growth Through Enhancing STAT3 Mediated ROS Production
title_sort galangin inhibits gastric cancer growth through enhancing stat3 mediated ros production
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109028/
https://www.ncbi.nlm.nih.gov/pubmed/33981228
http://dx.doi.org/10.3389/fphar.2021.646628
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