The natural compound GL22, isolated from Ganoderma mushrooms, suppresses tumor growth by altering lipid metabolism and triggering cell death.
The natural compound GL22, isolated from Ganoderma mushrooms, suppresses tumor growth by altering lipid metabolism and triggering cell death.
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从灵芝蘑菇中分离出来的天然化合物 GL22 通过改变脂质代谢和引发细胞死亡来抑制肿瘤生长
DOI：
10.1038/s41419-018-0731-6
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发表时间：
2018-06-07
影响因子：
9
通讯作者：
Sun C
中科院分区：
文献类型：
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作者：
Liu G;Wang K;Kuang S;Cao R;Bao L;Liu R;Liu H;Sun C
癌细胞重新连接它们的新陈代谢，以满足不受控制的增殖和生存的需求。脂代谢的重新编程支持肿瘤的生长、转移和治疗耐药。因此，靶向脂代谢重编程是一种潜在的癌症治疗策略。我们最近从中药白灵芝中分离到一个新的天然三萜化合物GL22。在这里，我们发现GL22在体外显著抑制肝癌细胞系Huh7.5的生长，并在体内显著抑制Huh7.5来源的异种肿瘤的生长。我们进一步发现，GL22诱导Huh7.5细胞线粒体功能障碍和细胞死亡，部分原因是脂肪酸固定和具有重要结构和代谢功能的线粒体脂质心磷脂的丢失。重要的是，我们证明GL22治疗降低了脂肪酸结合蛋白(FABP)的表达，这可能是心磷脂丢失、线粒体功能障碍和细胞死亡的基础。FABP的过表达可阻止GL22诱导的Huh7.5细胞死亡、心磷脂丢失、ATP生成减少和氧耗率降低。我们的结果支持通过操纵FABPs来靶向脂代谢作为一种癌症治疗策略，并促进中医药作为新型抗癌药物的重要来源。
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.
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影响因子：
4.7
作者：
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通讯作者：
Frohman, Michael A.
影响因子：
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影响因子：
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通讯作者：
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