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
N1 - Funding Information:
This work was supported by research grants from Taipei Medical University, Taipei Medical University Hospital, and Shuang Ho Hospital of Taiwan (TMU101-AE1-B25, TMU101-AE3-Y18 and 103TMU-SHH-02). The authors would like to thank the Office of Research and Development (Taipei Medicial University, Taipei, Taiwan) for the help in English editing.
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.
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U2 - 10.1038/srep06394
DO - 10.1038/srep06394
M3 - Article
C2 - 25227736
AN - SCOPUS:84923324365
SN - 2045-2322
VL - 4
JO - Scientific Reports
JF - Scientific Reports
M1 - 6394
ER -