Inonotus obliquus polysaccharides induces apoptosis of lung cancer cells and alters energy metabolism via the LKB1/AMPK axis.
The present study explores the mechanisms underlying the anti-cancer action of Inonotus obliquus polysaccharides (IOP). Thus, we characterized the IOP components extracted from Chaga sclerotium and, found that the extracts contained 70% polysaccharides with an average molecular weight of 4.5 × 104 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 mitochondrial 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 mitochondrial 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.
['Jiang|Shuping|S|', 'Shi|Fuli|F|', 'Lin|Hui|H|', 'Ying|Ying|Y|', 'Luo|Lingyu|L|', 'Huang|Deqiang|D|', 'Luo|Zhijun|Z|']
D000091162:AMP-Activated Protein Kinase Kinases D055372:AMP-Activated Protein Kinases D000255:Adenosine Triphosphate D000818:Animals D000970:Antineoplastic Agents D017209:Apoptosis D045744:Cell Line, Tumor D002470:Cell Survival D004734:Energy Metabolism D062610:Fungal Polysaccharides D006801:Humans D000084827:Inonotus D008297:Male D053078:Membrane Potential, Mitochondrial D051379:Mice D017346:Protein Serine-Threonine Kinases D015398:Signal Transduction
Inonotus obliquus polysaccharides Apoptosis Energy metabolism AMPK Tumorigenesis