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Int J Biol Macromol. 2019 Nov 18. pii: S0141-8130(19)32725-4. doi: 10.1016/j.ijbiomac.2019.10.174. [Epub ahead of print]

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

Author information

1
Jiangxi Provincial Key Laboratory of Tumor Pathogens and Molecular Pathology and Department of Pathophysiology, Nanchang University Jiangxi Medical College, China.
2
Department of Gastroenterology, Research Institute of Digestive Diseases, The First Affiliated Hospital, Nanchang University, Nanchang, China.
3
Jiangxi Provincial Key Laboratory of Tumor Pathogens and Molecular Pathology and Department of Pathophysiology, Nanchang University Jiangxi Medical College, China. Electronic address: zluo559914@ncu.edu.cn.

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 × 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.

KEYWORDS:

AMPK; Apoptosis; Energy metabolism; Inonotus obliquus polysaccharides; Tumorigenesis

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