Ganoderic acid A holds promising cytotoxicity on human glioblastoma mediated by incurring apoptosis and autophagy and inactivating PI3K/AKT signaling pathway.

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.

• Authors: Yong Cheng, Peng Xie
• Journal: Journal of biochemical and molecular toxicology (J Biochem Mol Toxicol) Vol. 33 Issue 11 Pg. e22392 (Nov 2019) ISSN: 1099-0461 [Electronic] United States
• PMID: 31503386 (Publication Type: Journal Article)
• Copyright: © 2019 Wiley Periodicals, Inc.

Chemical References

• CCND1 protein, human
• Cytotoxins
• Heptanoic Acids
• Cyclin D1
• Lanosterol
• ganoderic acid A
• MTOR protein, human
• Proto-Oncogene Proteins c-akt
• Ribosomal Protein S6 Kinases, 70-kDa
• TOR Serine-Threonine Kinases

Topics

• Apoptosis (drug effects)
• Autophagy (drug effects)
• Brain Neoplasms (metabolism, pathology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cyclin D1 (metabolism)
• Cytotoxins (pharmacology)
• Glioblastoma (metabolism, pathology)
• Heptanoic Acids (pharmacology)
• Humans
• Lanosterol (analogs & derivatives, pharmacology)
• Neoplasm Invasiveness
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)
• Reishi (chemistry)
• Ribosomal Protein S6 Kinases, 70-kDa (metabolism)
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (metabolism)