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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MDPI AG
2019-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/12/2338 |
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| author | Di Chen Yangmin Ma Peiqi Li Meng Liu Yuan Fang Jiejie Zhang Bilin Zhang Yuyu Hui Yue Yin |
| author_facet | Di Chen Yangmin Ma Peiqi Li Meng Liu Yuan Fang Jiejie Zhang Bilin Zhang Yuyu Hui Yue Yin |
| author_sort | Di Chen |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-13T05:31:47Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-13T05:31:47Z |
| publishDate | 2019-06-01 |
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| series | Molecules |
| spelling | doaj.art-a6eca291205a43728d45a09852ce2cac2022-12-21T23:58:02ZengMDPI AGMolecules1420-30492019-06-012412233810.3390/molecules24122338molecules24122338Piperlongumine Induces Apoptosis and Synergizes with Doxorubicin by Inhibiting the JAK2-STAT3 Pathway in Triple-Negative Breast CancerDi Chen0Yangmin Ma1Peiqi Li2Meng Liu3Yuan Fang4Jiejie Zhang5Bilin Zhang6Yuyu Hui7Yue Yin8Shaanxi Key Laboratory of Chemical Additives for Industry, Shaanxi University of Science and Technology, Xi’an 710021, ChinaShaanxi Key Laboratory of Chemical Additives for Industry, Shaanxi University of Science and Technology, Xi’an 710021, ChinaInstitute of Basic Medical Sciences, Xi’an Medical University, Xi’an 710021, ChinaInstitute of Basic Medical Sciences, Xi’an Medical University, Xi’an 710021, ChinaInstitute of Basic Medical Sciences, Xi’an Medical University, Xi’an 710021, ChinaInstitute of Basic Medical Sciences, Xi’an Medical University, Xi’an 710021, ChinaInstitute of Basic Medical Sciences, Xi’an Medical University, Xi’an 710021, ChinaShaanxi Key Laboratory of Chemical Additives for Industry, Shaanxi University of Science and Technology, Xi’an 710021, ChinaSchool of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an 710061, ChinaTriple-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.https://www.mdpi.com/1420-3049/24/12/2338triple-negative breast cancerpiperlonguminedoxorubicinapoptosisJAK2STAT3 |
| spellingShingle | Di Chen Yangmin Ma Peiqi Li Meng Liu Yuan Fang Jiejie Zhang Bilin Zhang Yuyu Hui Yue Yin Piperlongumine Induces Apoptosis and Synergizes with Doxorubicin by Inhibiting the JAK2-STAT3 Pathway in Triple-Negative Breast Cancer Molecules triple-negative breast cancer piperlongumine doxorubicin apoptosis JAK2 STAT3 |
| 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 | triple-negative breast cancer piperlongumine doxorubicin apoptosis JAK2 STAT3 |
| url | https://www.mdpi.com/1420-3049/24/12/2338 |
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