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Eupalinolide J Suppresses the Growth of Triple-Negative Breast Cancer Cells via Targeting STAT3 Signaling Pathway

Persistent activation of STAT3 plays an important role in the development of triple-negative breast cancer (TNBC), and suppression of STAT3 is considered as a novel approach for cancer therapy. In this project, we aimed to examine the anticancer activity and molecular mechanism of eupalinolide J (EJ...

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Autores principales: Lou, Chenghua, Chen, Yan, Zhang, Jie, Yang, Bo, Zhao, Huajun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761301/
https://www.ncbi.nlm.nih.gov/pubmed/31607920
http://dx.doi.org/10.3389/fphar.2019.01071
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author Lou, Chenghua
Chen, Yan
Zhang, Jie
Yang, Bo
Zhao, Huajun
author_facet Lou, Chenghua
Chen, Yan
Zhang, Jie
Yang, Bo
Zhao, Huajun
author_sort Lou, Chenghua
collection PubMed
description Persistent activation of STAT3 plays an important role in the development of triple-negative breast cancer (TNBC), and suppression of STAT3 is considered as a novel approach for cancer therapy. In this project, we aimed to examine the anticancer activity and molecular mechanism of eupalinolide J (EJ) in TNBC cells. The presented results demonstrated that the growth of human TNBC cells (MDA-MB-231 and MDA-MB-468 cells) was obviously inhibited by EJ. The IC(50) values were 3.74 ± 0.58 and 4.30 ± 0.39 μM, respectively. Further study demonstrated that EJ suppressed the proliferation of TNBC cells mainly through cell apoptosis induction, mitochondrial membrane potential (MMP) disruption, and cell cycle arrest. Meanwhile, the STAT3 and p-STAT3 in EJ-treated TNBC cells were remarkably suppressed. Importantly, silencing of STAT3 by STAT3-shRNA significantly blunted the anticancer activities of EJ in TNBC cells, suggesting that EJ suppressed cancer cell proliferation via targeting the STAT3 pathway. Notably, further study demonstrated that EJ significantly promoted the degradation of STAT3 in TNBC cells. Finally, EJ exhibited an effective antitumor activity against MDA-MB-231 cells in vivo. In conclusion, we identified that EJ suppressed the growth of TNBC cells via targeting the STAT3 signaling pathway. These results strongly support that EJ is a promising therapeutic agent for TNBC.
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spelling pubmed-67613012019-10-13 Eupalinolide J Suppresses the Growth of Triple-Negative Breast Cancer Cells via Targeting STAT3 Signaling Pathway Lou, Chenghua Chen, Yan Zhang, Jie Yang, Bo Zhao, Huajun Front Pharmacol Pharmacology Persistent activation of STAT3 plays an important role in the development of triple-negative breast cancer (TNBC), and suppression of STAT3 is considered as a novel approach for cancer therapy. In this project, we aimed to examine the anticancer activity and molecular mechanism of eupalinolide J (EJ) in TNBC cells. The presented results demonstrated that the growth of human TNBC cells (MDA-MB-231 and MDA-MB-468 cells) was obviously inhibited by EJ. The IC(50) values were 3.74 ± 0.58 and 4.30 ± 0.39 μM, respectively. Further study demonstrated that EJ suppressed the proliferation of TNBC cells mainly through cell apoptosis induction, mitochondrial membrane potential (MMP) disruption, and cell cycle arrest. Meanwhile, the STAT3 and p-STAT3 in EJ-treated TNBC cells were remarkably suppressed. Importantly, silencing of STAT3 by STAT3-shRNA significantly blunted the anticancer activities of EJ in TNBC cells, suggesting that EJ suppressed cancer cell proliferation via targeting the STAT3 pathway. Notably, further study demonstrated that EJ significantly promoted the degradation of STAT3 in TNBC cells. Finally, EJ exhibited an effective antitumor activity against MDA-MB-231 cells in vivo. In conclusion, we identified that EJ suppressed the growth of TNBC cells via targeting the STAT3 signaling pathway. These results strongly support that EJ is a promising therapeutic agent for TNBC. Frontiers Media S.A. 2019-09-19 /pmc/articles/PMC6761301/ /pubmed/31607920 http://dx.doi.org/10.3389/fphar.2019.01071 Text en Copyright © 2019 Lou, Chen, Zhang, Yang and Zhao 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). 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
Lou, Chenghua
Chen, Yan
Zhang, Jie
Yang, Bo
Zhao, Huajun
Eupalinolide J Suppresses the Growth of Triple-Negative Breast Cancer Cells via Targeting STAT3 Signaling Pathway
title Eupalinolide J Suppresses the Growth of Triple-Negative Breast Cancer Cells via Targeting STAT3 Signaling Pathway
title_full Eupalinolide J Suppresses the Growth of Triple-Negative Breast Cancer Cells via Targeting STAT3 Signaling Pathway
title_fullStr Eupalinolide J Suppresses the Growth of Triple-Negative Breast Cancer Cells via Targeting STAT3 Signaling Pathway
title_full_unstemmed Eupalinolide J Suppresses the Growth of Triple-Negative Breast Cancer Cells via Targeting STAT3 Signaling Pathway
title_short Eupalinolide J Suppresses the Growth of Triple-Negative Breast Cancer Cells via Targeting STAT3 Signaling Pathway
title_sort eupalinolide j suppresses the growth of triple-negative breast cancer cells via targeting stat3 signaling pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761301/
https://www.ncbi.nlm.nih.gov/pubmed/31607920
http://dx.doi.org/10.3389/fphar.2019.01071
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