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Piperlongumine Induces Apoptosis and Synergizes with Doxorubicin by Inhibiting the JAK2-STAT3 Pathway in Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) lacks major effective target molecules and chemotherapy remains the current main treatment. However, traditional chemotherapy drugs, such as doxorubicin (DOX), cause serious side effects and have a poor prognosis. Piperlongumine (PL), a natural alkaloid, has show...

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Autores principales: Chen, Di, Ma, Yangmin, Li, Peiqi, Liu, Meng, Fang, Yuan, Zhang, Jiejie, Zhang, Bilin, Hui, Yuyu, Yin, Yue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631638/
https://www.ncbi.nlm.nih.gov/pubmed/31242627
http://dx.doi.org/10.3390/molecules24122338
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author Chen, Di
Ma, Yangmin
Li, Peiqi
Liu, Meng
Fang, Yuan
Zhang, Jiejie
Zhang, Bilin
Hui, Yuyu
Yin, Yue
author_facet Chen, Di
Ma, Yangmin
Li, Peiqi
Liu, Meng
Fang, Yuan
Zhang, Jiejie
Zhang, Bilin
Hui, Yuyu
Yin, Yue
author_sort Chen, Di
collection PubMed
description Triple-negative breast cancer (TNBC) lacks major effective target molecules and chemotherapy remains the current main treatment. However, traditional chemotherapy drugs, such as doxorubicin (DOX), cause serious side effects and have a poor prognosis. Piperlongumine (PL), a natural alkaloid, has showed selective anticancer effects and is expected to become a new strategy against TNBC. In our research, cell viability, colony formation, flow cytometry, Western blot, and tumor xenograft model assays were established to evaluate the suppression effect of PL and DOX alone and in combination. Data showed that PL could effectively inhibit cell growth and induce apoptosis in two TNBC cell lines. We also demonstrated for the first time that the combination treatment of PL and DOX synergistically inhibited cell growth and induced apoptosis in TNBC cells. The suppression of STAT3 activation was indicated to be a mechanism of the anticancer effect. Moreover, the effectiveness of this combination was confirmed in a tumor xenograft model. These results revealed that inhibition of the JAK2-STAT3 pathway was a key anticancer mechanism when treated with PL alone or combined with DOX, suggesting that the combination of PL and chemotherapy drugs may be a potential strategy for the clinical treatment of TNBC.
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spelling pubmed-66316382019-08-19 Piperlongumine Induces Apoptosis and Synergizes with Doxorubicin by Inhibiting the JAK2-STAT3 Pathway in Triple-Negative Breast Cancer Chen, Di Ma, Yangmin Li, Peiqi Liu, Meng Fang, Yuan Zhang, Jiejie Zhang, Bilin Hui, Yuyu Yin, Yue Molecules Article Triple-negative breast cancer (TNBC) lacks major effective target molecules and chemotherapy remains the current main treatment. However, traditional chemotherapy drugs, such as doxorubicin (DOX), cause serious side effects and have a poor prognosis. Piperlongumine (PL), a natural alkaloid, has showed selective anticancer effects and is expected to become a new strategy against TNBC. In our research, cell viability, colony formation, flow cytometry, Western blot, and tumor xenograft model assays were established to evaluate the suppression effect of PL and DOX alone and in combination. Data showed that PL could effectively inhibit cell growth and induce apoptosis in two TNBC cell lines. We also demonstrated for the first time that the combination treatment of PL and DOX synergistically inhibited cell growth and induced apoptosis in TNBC cells. The suppression of STAT3 activation was indicated to be a mechanism of the anticancer effect. Moreover, the effectiveness of this combination was confirmed in a tumor xenograft model. These results revealed that inhibition of the JAK2-STAT3 pathway was a key anticancer mechanism when treated with PL alone or combined with DOX, suggesting that the combination of PL and chemotherapy drugs may be a potential strategy for the clinical treatment of TNBC. MDPI 2019-06-25 /pmc/articles/PMC6631638/ /pubmed/31242627 http://dx.doi.org/10.3390/molecules24122338 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Di
Ma, Yangmin
Li, Peiqi
Liu, Meng
Fang, Yuan
Zhang, Jiejie
Zhang, Bilin
Hui, Yuyu
Yin, Yue
Piperlongumine Induces Apoptosis and Synergizes with Doxorubicin by Inhibiting the JAK2-STAT3 Pathway in Triple-Negative Breast Cancer
title Piperlongumine Induces Apoptosis and Synergizes with Doxorubicin by Inhibiting the JAK2-STAT3 Pathway in Triple-Negative Breast Cancer
title_full Piperlongumine Induces Apoptosis and Synergizes with Doxorubicin by Inhibiting the JAK2-STAT3 Pathway in Triple-Negative Breast Cancer
title_fullStr Piperlongumine Induces Apoptosis and Synergizes with Doxorubicin by Inhibiting the JAK2-STAT3 Pathway in Triple-Negative Breast Cancer
title_full_unstemmed Piperlongumine Induces Apoptosis and Synergizes with Doxorubicin by Inhibiting the JAK2-STAT3 Pathway in Triple-Negative Breast Cancer
title_short Piperlongumine Induces Apoptosis and Synergizes with Doxorubicin by Inhibiting the JAK2-STAT3 Pathway in Triple-Negative Breast Cancer
title_sort piperlongumine induces apoptosis and synergizes with doxorubicin by inhibiting the jak2-stat3 pathway in triple-negative breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631638/
https://www.ncbi.nlm.nih.gov/pubmed/31242627
http://dx.doi.org/10.3390/molecules24122338
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