Guggulsterone inhibits migration and invasion through proteasomal and lysosomal degradation in human glioblastoma cells

Glioblastoma multiforme (GBM) is a deadly brain malignancy, and current therapies offer limited survival benefit. The phytosterol guggulsterone (GS) has been shown to exhibit antitumor efficacy. This study aimed to investigate the effects of GS on migration and invasion and its underlying mechanisms...

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Published in:European journal of pharmacology 2023-01, Vol.938, p.175411-175411, Article 175411
Main Authors: Yang, Jen-Fu, Chen, Tzu-Min, Chang, Hsin-Han, Tsai, Yu-Ling, Tsai, Wen-Chiuan, Huang, Wen-Yen, Lo, Cheng-Hsiang, Lin, Chun-Shu, Shen, Po-Chien, Chen, Ying
Format: Article
Language:English
Subjects:
Animals
Autophagy
Brain Neoplasms - pathology
Cathepsin B
Cell Line, Tumor
Cell Movement
Glioblastoma
Glioblastoma - pathology
Guggulsterone
Humans
Invasion
Lysosomes - metabolism
Matrix Metalloproteinase 2 - metabolism
Mice
Migration
Neoplasm Invasiveness
Proteasome Endopeptidase Complex - metabolism
Protein degradation
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Summary:Glioblastoma multiforme (GBM) is a deadly brain malignancy, and current therapies offer limited survival benefit. The phytosterol guggulsterone (GS) has been shown to exhibit antitumor efficacy. This study aimed to investigate the effects of GS on migration and invasion and its underlying mechanisms in human GBM cell lines. After GS treatment, the survival rate of GBM cells was reduced, and the migration and invasion abilities of GBM cells were significantly decreased. There was also concomitant decreased expression of focal adhesion complex, matrix metalloproteinase-2 (MMP2), MMP9 and cathepsin B. Furthermore, GS induced ERK phosphorylation and autophagy, with increased p62 and LC3B-II expression. Notably, treatment of in GBM cells with the proteasome inhibitor MG132 or the lysosome inhibitor NH4Cl reversed the GS-mediated inhibition of migration and invasion. In an orthotopic xenograft mouse model, immunohistochemical staining of brain tumor tissues demonstrated that MMP2 and cathepsin B expression was reduced in GS-treated mice. GS treatment inhibited GBM cell migration and invasion via proteasomal and lysosomal degradation, suggesting its therapeutic potential in clinical use in the future. [Display omitted]
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2022.175411