Inonotus obliquus polysaccharides induces apoptosis of lung cancer cells and alters energy metabolism via the LKB1/AMPK axis
Inonotus obliquus polysaccharides induces apoptosis of lung cancer cells and alters energy metabolism via the LKB1/AMPK axis
复制标题
桦褐孔菌多糖通过LKB1/AMPK轴诱导肺癌细胞凋亡并改变能量代谢
DOI：
10.1016/j.ijbiomac.2019.10.174
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发表时间：
2020-05-15
影响因子：
8.2
通讯作者：
Luo, Zhijun
中科院分区：
文献类型：
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作者：
Jiang, Shuping;Shi, Fuli;Luo, Zhijun
本研究探讨了刺耳菇多糖（IOP）的抗癌作用机制。因此，我们表征了从查加菌核中提取的IOP组分，发现提取物含有70%的多糖，平均分子量为4.5 × 10（4）Da，由75%的葡萄糖组成。然后，我们发现IOP提取物激活表达LKB 1的肺癌细胞中的AMPK，抑制细胞活力，集落形成，并引发细胞凋亡。同时，IOP下调Bcl-2，上调Bax，并增强Caspase-3和PARP的裂解。所有这些作用都可以通过用AMPK的化学抑制剂化合物C治疗来预防。IOP减少线粒体！膜电位（MMP），同时减少氧化磷酸化和糖酵解，这是依赖于LKB 1/AMPK。最后，50 mg/kg剂量的IOP显著抑制LLC 1细胞的同种异体移植肿瘤生长，并伴有细胞凋亡增加。总的来说，我们的研究结果表明IOP通过AMPK通过线粒体开放触发凋亡途径的机制作用于癌细胞！渗透性转换孔，并减少MMP，导致ATP产生抑制。因此，我们的研究为IOP作为一种有前途的替代或补充药物用于癌症治疗提供了坚实的基础。(C)2019由Elsevier B. V.出版
The present study explores the mechanisms underlying the anti-cancer action of lnonotus obliquus polysaccharides (IOP). Thus, we characterized the lOP components extracted from Chaga sclerotium and, found that the extracts contained 70% polysaccharides with an average molecular weight of 4.5 x 10(4) Da consisting of 75% glucose. We then showed that IOP extract activated AMPK in lung cancer cells expressing LKB1, suppressed cell viability, colony-formation, and triggered cell apoptosis. In conjunction, IOP downregulated Bcl-2, upregulated Bax, and enhanced cleavage of Caspase-3 and PARP. All of these effects were prevented by treatment with Compound C, a chemical inhibitor of AMPK. IOP diminished mitochondria! membrane potential (MMP), concurrent with decreases in oxidative phosphorylation and glycolysis, which was dependent on LKB1/AMPK. Finally, IOP at a dosage of 50 mg/kg significantly inhibited allograft tumor growth of the LLC1 cells in association with increased apoptosis. Collectively, our results demonstrate that IOP acts on cancer cells through a mechanism by which AMPK triggers the apoptotic pathway via the opening of mitochondria! permeability transition pore, and reducing MMP, leading to an inhibition of ATP production. Therefore, our study provides a solid foundation for the use of IOP as a promising alternative or supplementary medicine for cancer therapy. (C) 2019 Published by Elsevier B.V.