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Identification of Aloperine as an anti-apoptotic Bcl2 protein inhibitor in glioma cells.
PeerJ ; 7: e7652, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534865
ABSTRACT

OBJECTIVE:

Aloperine (ALO), an alkaloid isolated from the leaves of Sophora alopecuroides, has been suggested to exhibit anti-inflammatory and anti-tumor properties and is traditionally used to treat various human diseases, including cancer. However, limited information is available about the mechanisms that determine the anti-tumor activities of ALO.

METHODS:

Herein, through comprehensive bioinformatics methods and in vitro functional analyses, we evaluated the detailed anti-tumor mechanisms of ALO.

RESULTS:

Using the databases Bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine and PubChem Project, we identified the potential targets of ALO. A protein-protein interaction network was constructed to determine the relationship among these probable targets. Functional enrichment analysis revealed that ALO is potentially involved in the induction of apoptosis. In addition, molecular docking demonstrated that ALO expectedly docks into the active pocket of the Bcl2 protein, suggesting Bcl2 as a direct target of ALO. Moreover, western blot and qPCR analysis showed that ALO downregulated Bcl2 expression in human glioma cell lines, SK-N-AS and U118. Using flow cytometry methods, we further confirmed that ALO significantly promotes apoptosis in SK-N-AS and U118 cell lines, similar to the effect induced by ABT-737, a well-known Bcl2 inhibitor. In addition, Bcl-2 overexpression could rescue ALO-induced Bcl-2 inhibition and suppress pro-apoptotic effects in glioma cells.

CONCLUSION:

Taken together, these findings suggest that the natural agent ALO effectively enhances apoptosis by acting as a potential Bcl2 inhibitor in human glioma cells.

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Idioma: Inglês Revista: PeerJ Ano de publicação: 2019 Tipo de documento: Artigo País de afiliação: China