Nigericin Boosts Anti-Tumor Immune Response via Inducing Pyroptosis in Triple-Negative Breast Cancer
Although immune checkpoint inhibitors improved the clinical outcomes of advanced triple negative breast cancer (TBNC) patients, the response rate remains relatively low. Nigericin is an antibiotic derived from <i>Streptomyces hydrophobicus</i>. We found that nigericin caused cell death i...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/12/3221 |
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| author | Lisha Wu Shoumin Bai Jing Huang Guohui Cui Qingjian Li Jingshu Wang Xin Du Wenkui Fu Chuping Li Wei Wei Huan Lin Man-Li Luo |
| author_facet | Lisha Wu Shoumin Bai Jing Huang Guohui Cui Qingjian Li Jingshu Wang Xin Du Wenkui Fu Chuping Li Wei Wei Huan Lin Man-Li Luo |
| author_sort | Lisha Wu |
| collection | DOAJ |
| description | Although immune checkpoint inhibitors improved the clinical outcomes of advanced triple negative breast cancer (TBNC) patients, the response rate remains relatively low. Nigericin is an antibiotic derived from <i>Streptomyces hydrophobicus</i>. We found that nigericin caused cell death in TNBC cell lines MDA-MB-231 and 4T1 by inducing concurrent pyroptosis and apoptosis. As nigericin facilitated cellular potassium efflux, we discovered that it caused mitochondrial dysfunction, leading to mitochondrial ROS production, as well as activation of Caspase-1/GSDMD-mediated pyroptosis and Caspase-3-mediated apoptosis in TNBC cells. Notably, nigericin-induced pyroptosis could amplify the anti-tumor immune response by enhancing the infiltration and anti-tumor effect of CD4+ and CD8+ T cells. Moreover, nigericin showed a synergistic therapeutic effect when combined with anti-PD-1 antibody in TNBC treatment. Our study reveals that nigericin may be a promising anti-tumor agent, especially in combination with immune checkpoint inhibitors for advanced TNBC treatment. |
| first_indexed | 2024-03-09T03:23:59Z |
| format | Article |
| id | doaj.art-e5667dd9a81d45dbb744d2522820a9b3 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T03:23:59Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-e5667dd9a81d45dbb744d2522820a9b32023-12-03T15:05:33ZengMDPI AGCancers2072-66942023-06-011512322110.3390/cancers15123221Nigericin Boosts Anti-Tumor Immune Response via Inducing Pyroptosis in Triple-Negative Breast CancerLisha Wu0Shoumin Bai1Jing Huang2Guohui Cui3Qingjian Li4Jingshu Wang5Xin Du6Wenkui Fu7Chuping Li8Wei Wei9Huan Lin10Man-Li Luo11Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaDepartment of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaDepartment of Breast and Thyroid Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, ChinaSouth China National Bio-Safety Laboratory, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510600, ChinaDepartment of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaDepartment of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaDepartment of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaDepartment of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaDepartment of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaDepartment of Breast and Thyroid Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, ChinaDepartment of Breast Oncology, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510120, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaAlthough immune checkpoint inhibitors improved the clinical outcomes of advanced triple negative breast cancer (TBNC) patients, the response rate remains relatively low. Nigericin is an antibiotic derived from <i>Streptomyces hydrophobicus</i>. We found that nigericin caused cell death in TNBC cell lines MDA-MB-231 and 4T1 by inducing concurrent pyroptosis and apoptosis. As nigericin facilitated cellular potassium efflux, we discovered that it caused mitochondrial dysfunction, leading to mitochondrial ROS production, as well as activation of Caspase-1/GSDMD-mediated pyroptosis and Caspase-3-mediated apoptosis in TNBC cells. Notably, nigericin-induced pyroptosis could amplify the anti-tumor immune response by enhancing the infiltration and anti-tumor effect of CD4+ and CD8+ T cells. Moreover, nigericin showed a synergistic therapeutic effect when combined with anti-PD-1 antibody in TNBC treatment. Our study reveals that nigericin may be a promising anti-tumor agent, especially in combination with immune checkpoint inhibitors for advanced TNBC treatment.https://www.mdpi.com/2072-6694/15/12/3221nigericinimmune checkpoint inhibitorpyroptosisanti-tumor immune-responsetriple-negative breast cancer |
| spellingShingle | Lisha Wu Shoumin Bai Jing Huang Guohui Cui Qingjian Li Jingshu Wang Xin Du Wenkui Fu Chuping Li Wei Wei Huan Lin Man-Li Luo Nigericin Boosts Anti-Tumor Immune Response via Inducing Pyroptosis in Triple-Negative Breast Cancer Cancers nigericin immune checkpoint inhibitor pyroptosis anti-tumor immune-response triple-negative breast cancer |
| title | Nigericin Boosts Anti-Tumor Immune Response via Inducing Pyroptosis in Triple-Negative Breast Cancer |
| title_full | Nigericin Boosts Anti-Tumor Immune Response via Inducing Pyroptosis in Triple-Negative Breast Cancer |
| title_fullStr | Nigericin Boosts Anti-Tumor Immune Response via Inducing Pyroptosis in Triple-Negative Breast Cancer |
| title_full_unstemmed | Nigericin Boosts Anti-Tumor Immune Response via Inducing Pyroptosis in Triple-Negative Breast Cancer |
| title_short | Nigericin Boosts Anti-Tumor Immune Response via Inducing Pyroptosis in Triple-Negative Breast Cancer |
| title_sort | nigericin boosts anti tumor immune response via inducing pyroptosis in triple negative breast cancer |
| topic | nigericin immune checkpoint inhibitor pyroptosis anti-tumor immune-response triple-negative breast cancer |
| url | https://www.mdpi.com/2072-6694/15/12/3221 |
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