Ganoderma lucidum extract promotes tumor cell pyroptosis and inhibits metastasis in breast cancer. (April 2023)

• Record Type: Journal Article
• Authors: Zhong, Chunlian; Li, Yumei; Li, Wulin; lian, Shu; Li, Ye; Wu, Changhui; Zhang, Kun; Zhou, Guiyu; Wang, Weiyu; Xu, Huo; Huang, Mingqing; Katanaev, Vladimir; Jia, Lee; Lu, Yusheng
• Is Part Of: Food and chemical toxicology. Volume 174(2023)
• Publication Date: 2023-04
• Subjects: Ganoderma lucidum extract -- Pyroptotic cell death -- Gasdermin E -- Cytotoxic lymphocytes -- Tumor metastasis; GLE Ganoderma lucidum extract -- GSDME gasdermin E -- NK natural killer -- IL-1β interleukin-1β -- IL-18 interleukin-18 -- ICIs immune checkpoint inhibitors -- CAR chimeric antigen receptor -- HUVECs Human umbilical vein endothelial cells -- ROS reactive oxygen species -- RBC red blood cell -- HGB hematoglobin -- WBC white blood cell -- ECM endothelial cell culture medium; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2023.113654
• Languages: English
• ISSNs: 0278-6915

Abstract

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. Graphical abstract: Image 1 Highlights: GLE initiates breast cancer cell pyroptosis via caspase3-mediated cleavage of GSDME protein. GLE enhances anti-tumor immunity by unleashing NK and CD8 + T cells in local and system. GLE blocks multi-steps of tumor metastasis including adhesion, migration, invasion, colonization and angiogenesis.