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Ganoderic Acid A Holds Promising Cytotoxicity on Human Glioblastoma Mediated by Incurring Apoptosis and Autophagy and Inactivating PI3K/AKT Signaling Pathway

Ganoderic Acid A Holds Promising Cytotoxicity on Human Glioblastoma Mediated by Incurring Apoptosis and Autophagy and Inactivating PI3K/AKT Signaling Pathway

Yong Cheng, Peng Xie

J Biochem Mol Toxicol. 2019 Nov;33(11):e22392.

PMID: 31503386

Abstract:

Ganoderic acid A (GA-A), recognized as a lanostanetriterpene isolated from Ganoderma lucidum, demonstrates an efficient antitumor activity in multiple cancers. To date, it is unclear whether and how GA-A functions on human glioblastoma (GBM). To unravel the functional significance of GA-A on human glioblastoma (GBM), the cell-counting kit-8 and transwell assays were used to detect proliferation, migration, and invasion of human GBM cell after GA-A treatment. Then, we utilized the flow cytometry and western blot to further evaluate the effect of GA-A on GBM cell. Further, activities of autophagy and PI3K/AKT signaling were assessed by Western blot assay. We found that GA-A significantly inhibited proliferation, migration, and invasion of GBM cell. Additionally, GA-A markedly triggered cell apoptosis, which incarnated an elevation trend in apoptotic percentage, simultaneously, an increased level of proapoptosis protein (Bax and active caspase-3) and a decreased level of antiapoptosis protein (Bcl-2), induced by GA-A treatment. Meanwhile, levels of two well-known autophagy markers (beclin 1 and LC3 II) increased while another autophagic substrate (P-62) was reduced. Moreover, the expressions levels of phosphorylated AKT, mTOR, p-P70S6K, and cyclin D1 in the PI3K/AKT pathway were significantly reduced, which revealed GA-A repressed the activation of PI3K/AKT signaling pathway. Collectively, these results indicate that GA-A may encourage U251 cell growth and invasion/migration inhibition, apoptosis, and autophagy through the inactivation of PI3K/AKT signaling pathway in human GBM. Hence, GA-A may be a potent antitumorigenic agent for human GBM in future clinical practice.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP81907622	Ganoderic acid A		81907-62-2	Price

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