2. Academic Validation
  3. Nigericin Boosts Anti-Tumor Immune Response via Inducing Pyroptosis in Triple-Negative Breast Cancer

Nigericin Boosts Anti-Tumor Immune Response via Inducing Pyroptosis in Triple-Negative Breast Cancer

  • Cancers (Basel). 2023 Jun 16;15(12):3221. doi: 10.3390/cancers15123221.
Lisha Wu 1,  Shoumin Bai 1 2,  Jing Huang 3,  Guohui Cui 4,  Qingjian Li 1,  Jingshu Wang 1,  Xin Du 1,  Wenkui Fu 1,  Chuping Li 1,  Wei Wei 3,  Huan Lin 5,  Man-Li Luo 2 6
Affiliations

Affiliations

  • 1 Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
  • 2 Guangdong 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, China.
  • 3 Department of Breast and Thyroid Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, China.
  • 4 South China National Bio-Safety Laboratory, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510600, China.
  • 5 Department of Breast Oncology, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510120, China.
  • 6 Nanhai Translational Innovation Center of Precision Immunology, Sun Yat-sen Memorial Hospital, Foshan 528200, China.
PMID: 37370831 DOI: 10.3390/cancers15123221
Abstract

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 Streptomyces hydrophobicus. 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.

Keywords

anti-tumor immune-response; immune checkpoint inhibitor; nigericin; pyroptosis; triple-negative breast cancer.

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