The natural compound GL22, isolated from Ganoderma mushrooms, suppresses tumor growth by altering lipid metabolism and triggering cell death
| Autor: | Shan Kuang, Chaomin Sun, Rui Liu, Ruobing Cao, Kai Wang, Ge Liu, Hongwei Liu, Li Bao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Programmed cell death Cardiolipins Cell Survival Immunology Mice Nude Antineoplastic Agents Apoptosis Fatty Acid-Binding Proteins Models Biological Article Metastasis 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Adenosine Triphosphate Oxygen Consumption Cell Line Tumor medicine Cardiolipin Animals lcsh:QH573-671 Cell Proliferation Biological Products Mice Inbred BALB C Chemistry lcsh:Cytology Biphenyl Compounds Lipid metabolism Ganoderma Cell Biology Metabolism Lipid Droplets medicine.disease Lipid Metabolism Triterpenes Cell biology Mitochondria 030104 developmental biology Cell culture 030220 oncology & carcinogenesis Cancer cell Pyrazoles lipids (amino acids peptides and proteins) Reprogramming |
| Zdroj: | Cell Death and Disease, Vol 9, Iss 6, Pp 1-14 (2018) Cell Death & Disease |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-018-0731-6 |
| Popis: | Cancer cells rewire their metabolism to satisfy the demands of uncontrolled proliferation and survival. The reprogramming of lipid metabolism supports tumor growth, metastasis, and therapy-resistance. Therefore, targeting lipid metabolic reprogramming is a potential cancer treatment strategy. We recently isolated the novel natural triterpene GL22 from Ganoderma leucocontextum, a traditional Chinese medicine. Here, we show that GL22 significantly inhibits the growth of the liver cancer cell line Huh7.5 in vitro and of Huh7.5-derived tumor xenografts in vivo. We further find that GL22 induces mitochondrial dysfunction and cell death in Huh7.5 cells, in part due to fatty acid immobilization and loss of the mitochondrial lipid cardiolipin, which has vital structural and metabolic functions. Importantly, we demonstrate that GL22 treatment decreases the expression of fatty acid-binding proteins (FABPs), which likely underlies the loss of cardiolipin, mitochondrial dysfunction, and cell death. The over-expressions of FABPs prevented the GL22-induced cell death, loss of cardiolipin, decrease of ATP production, and reduction of oxygen consumption rate in Huh7.5 cells. Our results support targeting lipid metabolism via manipulating FABPs as a cancer treatment strategy, and promote Chinese medicine as an important source of novel anticancer drugs. |
| Databáze: | OpenAIRE |
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