Berberine, an Isoquinoline Alkaloid, Inhibits the Metastatic Potential of Breast Cancer Cells via Akt Pathway Modulation

Kuo, Han-Peng; Chuang, Tzu-Chao; Tsai, Shih‐Chang; Tseng, Hsiu-Hsueh; Hsu, Shang Wei; Chen, Yu Chang; Kuo, Chao‐Lin; Kuo, Yueh‐Hsiung; Liu, Jah‐Yao; Kao, Ming‐Ching

doi:10.1021/jf302832n

Cited by 75 publications

(49 citation statements)

References 26 publications

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“…In breast cancer cells, activation of the PI3K/Akt pathway has already been found to prevent cell apoptosis (27,36). By contrast, inhibition of janus kinase 2 (JAK2) promotes cell apoptosis (51,52).…”

Section: Discussionmentioning

confidence: 99%

“…The invasion ability of breast cancer cells was evaluated according to the methods described by Kuo et al (27). Briefly, 200 µl of MDA-MB-231 cells (1x10 6 cells in serum-free medium) were seeded onto the upper part of the 24-well Transwell chambers coated with Matrigel (BD Biosciences, San Jose, CA, uSA).…”

Section: Enzyme-linked Immunosorbent Assay (Elisa)mentioning

confidence: 99%

“…Coptis chinensis Franch (Huanglian), a medicinal herb, induces cell growth arrest and apoptosis in human breast cancer cells (26). Berberine, an active isoquino- (27). In the clinic, berberine hydrochloride (BER) with better water solubility than berberine, is used to treat gastrointestinal inflammation, bacterial diarrhea or infection as well as some gastrointestinal cancers (10,28,29).…”

Section: Introductionmentioning

confidence: 99%

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Berberine hydrochloride IL-8 dependently inhibits invasion and IL-8-independently promotes cell apoptosis in MDA-MB-231 cells

Zhao

Shi

et al. 2014

Oncology Reports

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Abstract. Breast cancer, the leading cause of cancer-related mortality worldwide in females, has high metastastic and recurrence rates. The aim of the present study was to evaluate the anti-metastatic and anticancer in situ effect of berberine hydrochloride (BER) in MDA-MB-231 cells. BER dose-dependently inhibited proliferation and the IL-8 secretion of MDA-MB-231 cells. Additional experiments revealed that the inactivation of PI3K, JAK2, NF-κB and AP-1 by BER contributed to the decreased IL-8 secretion. BER abrogated cell invasion induced by IL-8 accompanied with the downregulation of the gene expression of MMP-2, EGF, E-cadherin, bFGF and fibronectin.In addition, BER reduced cell motility but induced G2/M arrest and cell apoptosis in an IL-8-independent manner. BER modulated multiple signaling pathway molecules involved in the regulation of cell apoptosis, including activation of p38 MAPK and JNK and deactivation of JAK2, p85 PI3K, Akt and NF-κB. The enhanced cell apoptosis induced by BER was eliminated by inhibitors of p38 MAPK and JNK but was strengthened by activator of p38 MAPK. Thus, BER inhibited cell metastasis partly through the IL-8 mediated pathway while it induced G2/M arrest and promoted cell apoptosis through the IL-8 independent pathway. Apoptosis induced by BER was mediated by crosstalks of various pathways including activation of p38 MAPK and JNK pathways and inactivation of JAK2/ PI3K/NF-κB/AP-1 pathways. The results suggested that BER may be an efficient and safe drug candidate for treating highly metastatic breast cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Enzyme-linked Immunosorbent Assay (Elisa)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Berberine hydrochloride IL-8 dependently inhibits invasion and IL-8-independently promotes cell apoptosis in MDA-MB-231 cells

Zhao

Shi

et al. 2014

Oncology Reports

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“…Phosphorylation of XIAP by Akt protects XIAP protein from ubiquitination and results in XIAP protein stabilization [30]. Berberine inhibits cellular growth and promotes apoptosis by down-regulating the PI3K/Akt signaling pathway [31] and represses Akt protein expression by modulating the mRNA expression level and protein degradation of Akt [32]. Phosphorylation and subcellular distribution of MDM2 are regulated by the PI3K/Akt pathway [21].…”

Section: Discussionmentioning

confidence: 99%

Berberine Induces Apoptosis in p53-Null Leukemia Cells by Down-Regulating XIAP at the Post-Transcriptional Level

Liu

et al. 2013

Cell Physiol Biochem

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Background: Berberine exerts anticancer activities both in vitro and in vivo through different mechanisms. However, the underlying molecular mechanisms of berberine induced p53-independent apoptosis remain unclear. Methods: The p53-null leukemia cell line EU-4 cells were exposed to berberine. Then the cell viability and apoptosis were determined. Western blot and PCR were employed to detect the expression of apoptosis related protein, XIAP and MDM2. Small interfering RNA (siRNA) was applied to knock down endogenous expression of MDM2 and XIAP. Results: Berberine induced p53-independent, XIAP-mediated apoptotic cell death in p53-null leukemia cells. Treatment with berberine resulted in suppression of XIAP protein in a dose- and time- dependent manner. Berberine induced down-regulation of XIAP protein involving inhibition of MDM2 expression and a proteasome-dependent pathway. Moreover, inhibition of XIAP by berberine or siRNA increased the sensitivity of leukemia cells to doxorubicin-induced apoptosis. Conclusion: Our findings characterize the molecular mechanisms of berberine-induced caspase activation and subsequent apoptosis, and berberine may be a novel candidate inducer of apoptosis in leukemia cells, which normally lack p53 expression.

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“…Suppression of gene transcription [58], reactive oxygen species mechanisms [59], mitochondrial and caspase pathways [60], anti-calmodulin property [61] inhibition of key kinase enzymes [62], and many other multiple mechanisms [63] have been suggested as the possible mode of action for berberine-induced apoptosis in cancer cells. Inhibition of cancer metastasis through downregulation of activities and expression levels of key enzymes, such as heparanse [64] and matrix metalloproteinases 2 and 9 [65], are also among the various anticancer study reports on berberine.…”

Section: Case Example 1-berberis Darwiniimentioning

confidence: 99%

The Hidden Treasure in Europe?s Garden Plants: Case Examples; Berberis darwinni and Berginia cordifolia

Habtemariam¹

2012

Med Aromat Plants

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Berberine, an Isoquinoline Alkaloid, Inhibits the Metastatic Potential of Breast Cancer Cells via Akt Pathway Modulation

Cited by 75 publications

References 26 publications

Berberine hydrochloride IL-8 dependently inhibits invasion and IL-8-independently promotes cell apoptosis in MDA-MB-231 cells

Berberine hydrochloride IL-8 dependently inhibits invasion and IL-8-independently promotes cell apoptosis in MDA-MB-231 cells

Berberine Induces Apoptosis in p53-Null Leukemia Cells by Down-Regulating XIAP at the Post-Transcriptional Level

The Hidden Treasure in Europe?s Garden Plants: Case Examples; Berberis darwinni and Berginia cordifolia

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