A gene expression signature-based approach reveals the mechanisms of action of the Chinese herbal medicine berberine

Kuen Haur Lee, Hsiang Ling Lo, Wan Chun Tang, Heidi Hao Yun Hsiao, Pei Ming Yang

研究成果: 雜誌貢獻文章

27 引文 (Scopus)

摘要

Berberine (BBR), a traditional Chinese herbal medicine, was shown to display anticancer activity. In this study, we attempted to provide a global view of the molecular pathways associated with its anticancer effect through a gene expression-based chemical approach. BBR-induced differentially expressed genes obtained from the Gene Expression Omnibus (GEO) at the National Center for Biotechnology Information (NCBI) were analyzed using the Connectivity Map (CMAP) database to compare similarities of gene expression profiles between BBR and CMAP compounds. Candidate compounds were further analyzed using the Search Tool for Interactions of Chemicals (STITCH) database to explore chemical-protein interactions. Results showed that BBR may inhibit protein synthesis, histone deacetylase (HDAC), or AKT/mammalian target of rapamycin (mTOR) pathways. Further analyses demonstrated that BBR inhibited global protein synthesis and basal AKT activity, and induced endoplasmic reticulum (ER) stress and autophagy, which was associated with activation of AMP-activated protein kinase (AMPK). However, BBR did not alter mTOR or HDAC activities. Interestingly, BBR induced the acetylation of α -tubulin, a substrate of HDAC6. In addition, the combination of BBR and SAHA, a pan-HDAC inhibitor, synergistically inhibited cell proliferation and induced cell cycle arrest. Our results provide novel insights into the mechanisms of action of BBR in cancer therapy.
原文英語
文章編號6394
期刊Scientific Reports
4
DOIs
出版狀態已發佈 - 2014

指紋

Berberine
Herbal Medicine
Transcriptome
Histone Deacetylases
Sirolimus
Chemical Databases
Gene Expression
Information Centers
Proteins
AMP-Activated Protein Kinases
Endoplasmic Reticulum Stress
Histone Deacetylase Inhibitors
Autophagy
Tubulin
Acetylation
Biotechnology
Cell Cycle Checkpoints
Cell Proliferation
Databases

ASJC Scopus subject areas

  • General

引用此文

A gene expression signature-based approach reveals the mechanisms of action of the Chinese herbal medicine berberine. / Lee, Kuen Haur; Lo, Hsiang Ling; Tang, Wan Chun; Hsiao, Heidi Hao Yun; Yang, Pei Ming.

於: Scientific Reports, 卷 4, 6394, 2014.

研究成果: 雜誌貢獻文章

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abstract = "Berberine (BBR), a traditional Chinese herbal medicine, was shown to display anticancer activity. In this study, we attempted to provide a global view of the molecular pathways associated with its anticancer effect through a gene expression-based chemical approach. BBR-induced differentially expressed genes obtained from the Gene Expression Omnibus (GEO) at the National Center for Biotechnology Information (NCBI) were analyzed using the Connectivity Map (CMAP) database to compare similarities of gene expression profiles between BBR and CMAP compounds. Candidate compounds were further analyzed using the Search Tool for Interactions of Chemicals (STITCH) database to explore chemical-protein interactions. Results showed that BBR may inhibit protein synthesis, histone deacetylase (HDAC), or AKT/mammalian target of rapamycin (mTOR) pathways. Further analyses demonstrated that BBR inhibited global protein synthesis and basal AKT activity, and induced endoplasmic reticulum (ER) stress and autophagy, which was associated with activation of AMP-activated protein kinase (AMPK). However, BBR did not alter mTOR or HDAC activities. Interestingly, BBR induced the acetylation of α -tubulin, a substrate of HDAC6. In addition, the combination of BBR and SAHA, a pan-HDAC inhibitor, synergistically inhibited cell proliferation and induced cell cycle arrest. Our results provide novel insights into the mechanisms of action of BBR in cancer therapy.",
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AU - Yang, Pei Ming

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