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

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish
Article number6394
JournalScientific Reports
Volume4
DOIs
Publication statusPublished - 2014

Fingerprint

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

Cite this

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.

In: Scientific Reports, Vol. 4, 6394, 2014.

Research output: Contribution to journalArticle

@article{779ae3928861430395e9e18636347f13,
title = "A gene expression signature-based approach reveals the mechanisms of action of the Chinese herbal medicine berberine",
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.",
author = "Lee, {Kuen Haur} and Lo, {Hsiang Ling} and Tang, {Wan Chun} and Hsiao, {Heidi Hao Yun} and Yang, {Pei Ming}",
year = "2014",
doi = "10.1038/srep06394",
language = "English",
volume = "4",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - A gene expression signature-based approach reveals the mechanisms of action of the Chinese herbal medicine berberine

AU - Lee, Kuen Haur

AU - Lo, Hsiang Ling

AU - Tang, Wan Chun

AU - Hsiao, Heidi Hao Yun

AU - Yang, Pei Ming

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84923324365&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923324365&partnerID=8YFLogxK

U2 - 10.1038/srep06394

DO - 10.1038/srep06394

M3 - Article

VL - 4

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 6394

ER -