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Ganoderma lucidum extract promotes tumor cell pyroptosis and inhibits metastasis in breast cancer
Chunlian Zhong1, Yumei Li2, Wulin Li1
1Fujian-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.
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.
Insights
Ganoderma lucidum extract (GLE) triggers pyroptosis, a form of inflammatory cell death, in breast cancer cells. This extract also enhances anti-tumor immunity and inhibits cancer metastasis, offering a potential new cancer treatment.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Tumor cell death regulation is crucial for cancer treatment.
- Tumor resistance to cell death necessitates novel therapeutic strategies.
- Pyroptosis, an inflammatory cell death pathway, presents a potential avenue for enhancing tumor cell death.
Purpose of the Study:
- To investigate the role of Ganoderma lucidum extract (GLE) in inducing pyroptotic cell death in breast cancer.
- To elucidate the molecular mechanisms underlying GLE-induced pyroptosis.
- To evaluate the effects of GLE on anti-tumor immunity and cancer metastasis.
Main Methods:
- Breast cancer cells were treated with varying concentrations of GLE (50-200 μg/mL).
- Reactive oxygen species (ROS) levels, pyroptosis markers, and immune cell populations (NK and CD8+ T cells) were assessed.
- Mechanisms involving caspase 3 and gasdermin E (GSDME) cleavage were analyzed.
- Inhibition of tumor metastasis steps (adhesion, migration, invasion, colonization, angiogenesis) was evaluated.
Main Results:
- GLE treatment significantly increased ROS levels and induced pyroptotic cell death in breast cancer cells.
- GLE activated caspase 3, leading to GSDME cleavage and pore formation, releasing inflammatory factors.
- GLE enhanced anti-tumor immune responses by increasing NK and CD8+ T cell subsets.
- GLE demonstrated inhibitory effects on multiple stages of tumor metastasis.
Conclusions:
- Ganoderma lucidum extract (GLE) effectively induces pyroptosis in breast cancer cells.
- GLE exhibits potential as a therapeutic agent by enhancing anti-tumor immunity and suppressing metastasis.
- GLE may serve as a complementary treatment alongside chemotherapy or immunotherapy for metastatic breast cancer.
