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Updated: Feb 9, 2026
Analysis of Human Natural Killer Cell Metabolism
Published on: June 22, 2020
The natural compound GL22, isolated from Ganoderma mushrooms, suppresses tumor growth by altering lipid metabolism
Ge Liu1,2,3, Kai Wang3,4, Shan Kuang1,2
1CAS Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, China.
Abstract:
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.
Insights
A novel compound from traditional Chinese medicine, GL22, inhibits liver cancer growth by disrupting lipid metabolism and causing mitochondrial dysfunction. Targeting fatty acid-binding proteins (FABPs) offers a new therapeutic strategy.
Area of Science:
- Oncology
- Metabolic pathways
- Pharmacology
Background:
- Cancer cells exhibit altered metabolism, including lipid reprogramming, which fuels tumor growth and resistance.
- Targeting aberrant lipid metabolism presents a promising strategy for cancer therapy.
- Traditional Chinese medicine is a valuable source of novel therapeutic compounds.
Purpose of the Study:
- To investigate the anticancer effects of the novel triterpene GL22, isolated from Ganoderma leucocontextum.
- To elucidate the mechanism of action of GL22 in liver cancer cells, focusing on lipid metabolism.
- To evaluate GL22 as a potential therapeutic agent for liver cancer.
Main Methods:
- In vitro studies using the liver cancer cell line Huh7.5.
- In vivo studies using Huh7.5-derived tumor xenografts.
- Analysis of mitochondrial function, cardiolipin levels, fatty acid-binding protein (FABP) expression, ATP production, and oxygen consumption rate.
Main Results:
- GL22 significantly inhibited Huh7.5 liver cancer cell growth in vitro and in vivo.
- GL22 induced mitochondrial dysfunction and cell death by immobilizing fatty acids and reducing cardiolipin levels.
- GL22 decreased FABP expression, and FABP overexpression protected cells from GL22-induced toxicity.
Conclusions:
- GL22 demonstrates potent anticancer activity against liver cancer by targeting lipid metabolism and mitochondrial function.
- Manipulation of FABPs represents a viable strategy for cancer treatment.
- Ganoderma leucocontextum and its compounds hold potential as sources for novel anticancer drugs.
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