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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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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. |
format | Online Article Text |
id | pubmed-8109028 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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