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  3. Ganoderma lucidum extract-mediated gasdermin E cleavage promotes tumor cell pyroptosis and inhibits metastasis in breast cancer

Ganoderma lucidum extract-mediated gasdermin E cleavage promotes tumor cell pyroptosis and inhibits metastasis in breast cancer

  • Food Chem Toxicol. 2023 Feb 7;113654. doi: 10.1016/j.fct.2023.113654.
Chunlian Zhong 1,  Yumei Li 2,  Wulin Li 1,  Shu Lian 1,  Ye Li 3,  Changhui Wu 3,  Kun Zhang 3,  Guiyu Zhou 1,  Weiyu Wang 4,  Huo Xu 1,  Mingqing Huang 5,  Vladimir Katanaev 6,  Lee Jia 7,  Yusheng Lu 8
Affiliations

Affiliations

  • 1 Fujian-Taiwan-Hongkong-Macao Science and Technology Cooperation Base of Intelligent Pharmaceutics, College of Materials and Chemical Engineering, Minjiang University, Fuzhou, Fujian, 350108, China; Fuzhou Institute of Oceanography, Minjiang University, Fuzhou, Fujian, 350108, China.
  • 2 School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China.
  • 3 Fujian Xianzhilou Biological and Technology Co., Ltd., Fuzhou, China.
  • 4 Fujian-Taiwan-Hongkong-Macao Science and Technology Cooperation Base of Intelligent Pharmaceutics, College of Materials and Chemical Engineering, Minjiang University, Fuzhou, Fujian, 350108, China; Fuzhou Institute of Oceanography, Minjiang University, Fuzhou, Fujian, 350108, China; College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China.
  • 5 College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China.
  • 6 Fujian-Taiwan-Hongkong-Macao Science and Technology Cooperation Base of Intelligent Pharmaceutics, College of Materials and Chemical Engineering, Minjiang University, Fuzhou, Fujian, 350108, China; Translational Research Center in Oncohaematology, Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
  • 7 Fujian-Taiwan-Hongkong-Macao Science and Technology Cooperation Base of Intelligent Pharmaceutics, College of Materials and Chemical Engineering, Minjiang University, Fuzhou, Fujian, 350108, China; Fuzhou Institute of Oceanography, Minjiang University, Fuzhou, Fujian, 350108, China. Electronic address: [email protected].
  • 8 Fujian-Taiwan-Hongkong-Macao Science and Technology Cooperation Base of Intelligent Pharmaceutics, College of Materials and Chemical Engineering, Minjiang University, Fuzhou, Fujian, 350108, China; Fuzhou Institute of Oceanography, Minjiang University, Fuzhou, Fujian, 350108, China. Electronic address: [email protected].
PMID: 36758785 DOI: 10.1016/j.fct.2023.113654
Abstract

Regulation of tumor cell death is a fundamental mechanism for tumor treatment. However, most tumors are resistant to cell death. Triggering inflammatory cell death, Pyroptosis, may provide a new view of enhancing tumor cell death. Here we report a new role of Ganoderma lucidum extract (GLE) in pyroptotic cell death. Treatment with GLE (50-200 μg/mL) significantly elevated Reactive Oxygen Species (ROS) levels and caused pyroptotic cell death in breast Cancer cells. Mechanistically, GLE activates Caspase 3 and further cleaves the gasdermin E (GSDME) protein to form pores on the cell membrane, releasing massive amounts of inflammatory factors in breast Cancer cells. We also showed that GLE enhanced antitumor immune responses by substantially increasing the subsets of natural killer (NK) and CD8+T cells in the peripheral immune system and tumor microenvironment. In addition, GLE destroys multiple steps of tumor metastasis, including adhesion, migration, invasion, colonization, and angiogenesis. Collectively, these results suggest that GLE provides a potential approach for breast Cancer treatment, which may complement chemotherapy or immunotherapy for Cancer metastasis.

Keywords

Cytotoxic lymphocytes; Ganoderma lucidum extract; Gasdermin E; Pyroptotic cell death; Tumor metastasis.

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