Targets and mechanisms of berberine, a natural drug with potential to treat cancer with special focus on breast cancer

Kaboli, Parham Jabbarzadeh; Rahmat, Asmah; Ismail, Patimah; Ling, King-Hwa

doi:10.1016/j.ejphar.2014.06.025

Cited by 124 publications

(63 citation statements)

References 94 publications

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“…We further explored the molecular mechanism underlying the anti‐lung cancer efficacy of BBR, studies observed signalling pathways and potential targets that were involved in the anti‐cancer responses of BBR in different cancer types . We previously showed that BBR inhibited proliferation and induced apoptosis of NSCLC cells through p38α MAPK‐mediated increase in p53 and FOXO3a expressions .…”

Section: Discussionmentioning

confidence: 99%

The enhancement of combination of berberine and metformin in inhibition of DNMT1 gene expression through interplay of SP1 and PDPK1

Zheng

Tang

et al. 2017

J Cellular Molecular Medi

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Berberine (BBR), one of active alkaloid found in the rhizome, exhibited anti‐cancer properties. We have showed that BBR inhibited growth of non‐small cell lung cancer (NSCLC) cells through mitogen‐activated protein kinase (MAPK)‐mediated increase in forkhead box O3a (FOXO3a). However, the in‐depth mechanism underlying the anti‐tumor effects still remained to be elucidated. Herein, we further confirmed that BBR not only induced cell cycle arrest, but also reduced migration and invasion of NSCLC cells. Mechanistically, we observed that BBR reduced 3‐phosphoinositide‐dependent protein kinase‐1 (PDPK1) and transcription factor SP1 protein expressions. Exogenously expressed SP1 overcame BBR‐inhibited PDPK1 expression. Moreover, BBR inhibited DNA methyltransferase 1 (DNMT1) gene expression and overexpressed DNMT1 resisted BBR‐inhibited cell growth. Intriguingly, overexpressed PDPK1 antagonized BBR‐inhibited SP1 and DNMT1 expressions. Finally, metformin enhanced the effects of BBR both in vitro and in vivo. Collectively, we observe that BBR inhibits proliferation of NSCLC cells through inhibition of SP1 and PDPK1; this results in a reduction of DNMT1 expression. The interplay of PDPK1 and SP1 contributes to the inhibition of DNMT1 in response to BBR. In addition, there is a synergy of BBR and metformin. This study uncovers a new mechanism of BBR in combination with metformin for NSCLC‐associated therapy.

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Section: Discussionmentioning

confidence: 99%

The enhancement of combination of berberine and metformin in inhibition of DNMT1 gene expression through interplay of SP1 and PDPK1

Zheng

Tang

et al. 2017

J Cellular Molecular Medi

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“…Although BBR is regarded as a potential therapeutic drug for breast cancer, a better understanding of genes and cellular pathways regulated by BBR is needed to define the mechanisms of its action in cancer treatment39. A recent study also performed genome-wide expression profiling of BBR-treated human breast cancer cells (MCF-7 and MDA-MB-231 cells) using complementary DNA (cDNA) microarrays40.…”

Section: Discussionmentioning

confidence: 99%

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

Lee

Tang

et al. 2014

Sci Rep

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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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“…The molecular targets of berberine's antitumor activity include p53, AKT, MAPK, STAT3 and NFκB, which can monitor the cell cycle, apoptosis, tumor angiogenesis, and invasion [7]. Berberine also suppresses the activation of some cell growth factor receptors such as EGFR, ERBB2, and VEGF [8]. …”

Section: Introductionmentioning

confidence: 99%

Berberine inhibits EGFR signaling and enhances the antitumor effects of EGFR inhibitors in gastric cancer

et al. 2016

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Cetuximab plus chemotherapy for advanced gastric cancer (GC) shows an active result in phase 2 trials. Unfortunately, Combination of cetuximab does not provide enough benefit to chemotherapy alone in phase 3 trials. Studies have demonstrated that berberine can suppress the activation of EGFR in tumors. In this study, we evaluated whether berberine could enhance the effects of EGFR-TKIs in GC cell lines and xenograft models. Our data suggest that berberine could effectively enhance the activity of erlotinib and cetuximab in vitro and in vivo. Berberine was found to inhibit growth in GC cell lines and to induce apoptosis. These effects were linked to inhibition of EGFR signaling activation, including the phosphorylation of STAT3. The expressions of Bcl-xL and Cyclind1 proteins were decreased, whereas the levels of cleavage of poly-ADP ribose polymerase (PARP) were considerably increased in the cell lines in response to berberine treatment. These results suggest a potential role for berberine in the treatment of GC, particularly in combination with EGFR-TKIs therapy. Berberine may be a competent therapeutic agent in GC where it can enhance the effects of EGFR inhibitors.

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Targets and mechanisms of berberine, a natural drug with potential to treat cancer with special focus on breast cancer

Cited by 124 publications

References 94 publications

The enhancement of combination of berberine and metformin in inhibition of DNMT1 gene expression through interplay of SP1 and PDPK1

The enhancement of combination of berberine and metformin in inhibition of DNMT1 gene expression through interplay of SP1 and PDPK1

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

Berberine inhibits EGFR signaling and enhances the antitumor effects of EGFR inhibitors in gastric cancer

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