Growth Suppression of HER2-Overexpressing Breast Cancer Cells by Berberine via Modulation of the HER2/PI3K/Akt Signaling Pathway

Kuo, Han-Peng; Chuang, Tzu-Chao; Yeh, Ming‐Yang; Hsu, Shang Wei; Way, Tzong‐Der; Chen, Po‐Yuan; Wang, Shan‐Shue; Chang, Yung‐Hsien; Kao, Ming‐Ching; Liu, Jah‐Yao

doi:10.1021/jf2012584

Cited by 71 publications

(54 citation statements)

References 35 publications

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“…35) Suppression of the EGFR signaling pathway by berberine has been reported by several groups. 31,36,37) Berberine inhibited growth and promoted apoptosis of breast cancer cells 38) and the mechanism was shown to be via inhibition of the HER2 signaling pathway. This evidence suggests the inhibition of ERK upstream stimuli, EGFR and HER2 being the mechanism by which berberine affected the ERK pathway as observed in the current study.…”

Section: )mentioning

confidence: 99%

Berberine Induces Cell Cycle Arrest in Cholangiocarcinoma Cell Lines <i>via</i> Inhibition of NF-κB and STAT3 Pathways

Puthdee

Seubwai

Vaeteewoottacharn

et al. 2017

Biological & Pharmaceutical Bulletin

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Berberine is a natural compound found in several herbs. Anticancer activity of berberine was reported in several cancers, however, little is known regarding the effects of berberine against cholangiocarcinoma (CCA). In this study, the growth inhibitory effects of berberine on CCA cell lines and its molecular mechanisms were explored. Cell growth and cell cycle distribution were examined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. The expression levels of cell cycle regulatory proteins were determined by Western blot analysis. Berberine significantly inhibited growth of CCA cell lines in a dose and time dependent fashion. The inhibition was largely attributed to cell cycle arrest at the G1 phase through the reduction of cyclin D1, and cyclin E. Moreover, berberine could reduce the expression and activation of signal transducers and activator of transcription 3 (STAT3) and probably nuclear factor-kappaB (NF-κB) via suppression of extracellular signal-regulated kinase (ERK) 1/2 action. These results highlight the potential of berberine to be a multi-target agent for CCA treatment.

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Section: )mentioning

confidence: 99%

Berberine Induces Cell Cycle Arrest in Cholangiocarcinoma Cell Lines <i>via</i> Inhibition of NF-κB and STAT3 Pathways

Puthdee

Seubwai

Vaeteewoottacharn

et al. 2017

Biological & Pharmaceutical Bulletin

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“…BBR has multiple pharmacological properties including antioxidant, anti-apoptotic, and anticancer effects and activity against obesity and Alzheimer’s disease [13-16]. BBR affects cancer cell proliferation with consequent impairment of cell division through downregulation of cyclin B1 and upregulation of p21 in a variety of cancer types, including lung and breast cancer cells [17-19].…”

Section: Introductionmentioning

confidence: 99%

“…BBR affects cancer cell proliferation with consequent impairment of cell division through downregulation of cyclin B1 and upregulation of p21 in a variety of cancer types, including lung and breast cancer cells [17-19]. In addition, BBR triggers pro-apoptotic effects through suppression of the HER2/PI3K/AKT signaling pathway [16]. We also reported that inhibition of AP-1 transcriptional activity by BBR treatment suppresses invasion of breast cancer cells [20].…”

Section: Introductionmentioning

confidence: 99%

Berberine Suppresses Cell Motility Through Downregulation of TGF-β1 in Triple Negative Breast Cancer Cells

Kim

Lee

You

et al. 2018

Cell Physiol Biochem

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Background/Aims: Transforming growth factor-beta proteins (TGF-βs) are multifunctional growth factors and powerful modulators of the epithelial-mesenchymal transition (EMT) in a variety of cancer types including breast and lung cancer cells. Here, we demonstrated the inhibitory effect of berberine (BBR) on tumor growth and metastasis of triple negative breast cancer (TNBC) cells via suppression of TGF-β1 expression. Methods: The levels of mRNA expression were analyzed by real-time PCR. The levels of MMP-2, MMP-9 and TGF-β1 protein expression were analyzed by zymography and confocal microscopy, respectively. Cell migration was analyzed by wound healing assay. Tumorigenicity of TNBC cells such as tumor growth and metastasis was analyzed using xenograft models. Results: In a clinical data set, aberrant TGF-β1 expression was associated with poor prognosis of breast cancer patients. Our in vitro results using TNBC cells showed that the expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 and the capacity for cell migration were increased by TGF-β1 treatment. In contrast, basal levels of MMP-2 and MMP-9 were suppressed by a specific TGF-β receptor I inhibitor, SB431542. In addition, TGF-β1–induced MMP-2 and MMP-9 expression and cell migration were decreased by SB431542. Interestingly, we showed for the first time that BBR decreased the level of TGF-β1, but not TGF-β2, in TNBC cells. Furthermore, BBR significantly decreased the level of MMP-2 expression as well as the capacity for cell migration in TNBC cells. Finally, we examined the effect of BBR on in vivo tumor growth and lung metastasis in MDA-MB231 and 4T1 breast cancer xenograft models and showed that both were significantly decreased following BBR treatment. Conclusion: BBR suppresses tumorigenicity of TNBC cells through inhibition of TGF-β1 expression. Therefore, we demonstrate that BBR could be a promising drug for treatment of TNBC.

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“…Induction of apoptosis of cancer cells, mainly through the mitochondrial-and death receptor-dependent pathways, is the principal strategy for chemotherapy. In addition, several other pathways involved in cell apoptosis are influenced by chemotherapeutic drugs (31)(32)(33). Berberine has been demonstrated to induce apoptosis of cancer cells including SW60 and HepG2 cells by interfering with the expression of molecules in pathways including Bcl-2, Bax and caspase-3 (34)(35)(36).…”

Section: Introductionmentioning

confidence: 99%

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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Growth Suppression of HER2-Overexpressing Breast Cancer Cells by Berberine via Modulation of the HER2/PI3K/Akt Signaling Pathway

Cited by 71 publications

References 35 publications

Berberine Induces Cell Cycle Arrest in Cholangiocarcinoma Cell Lines <i>via</i> Inhibition of NF-κB and STAT3 Pathways

Berberine Induces Cell Cycle Arrest in Cholangiocarcinoma Cell Lines <i>via</i> Inhibition of NF-κB and STAT3 Pathways

Berberine Suppresses Cell Motility Through Downregulation of TGF-β1 in Triple Negative Breast Cancer Cells

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

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