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Abstract Title:

Inonotus obliquus polysaccharides induces apoptosis of lung cancer cells and alters energy metabolism via the LKB1/AMPK axis.

Abstract Source:

Int J Biol Macromol. 2019 Nov 18. Epub 2019 Nov 18. PMID: 31751687

Abstract Author(s):

Shuping Jiang, Fuli Shi, Hui Lin, Ying Ying, Lingyu Luo, Deqiang Huang, Zhijun Luo

Article Affiliation:

Shuping Jiang

Abstract:

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 × 10 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.

Study Type : In Vitro Study

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