Berberine Suppresses the TPA-Induced MMP-1 and MMP-9 Expressions Through the Inhibition of PKC-α in Breast Cancer Cells

Kim, Sang-Min; Han, Jeonghun; Lee, Se Kyung; Choi, Moon Young; Kim, Jiyoung; Lee, Jeonghui; Jung, Seung Pil; Kim, Jee Soo; Kim, Jung Han; Choe, Jun Ho; Lee, Jeong Eon; Nam, Seok Jin

doi:10.1016/j.jss.2011.11.1041

Cited by 56 publications

(36 citation statements)

References 33 publications

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“…1C). Recently, we reported that the level of MMP-1 expression was increased by TPA in breast cancer cells [8]. So, we confirmed as positive control that the MMP-1 protein expression was increased by TPA treatment in cell culture media (Fig.…”

Section: Resultssupporting

confidence: 73%

“…BBR induces cell cycle arrest in the G1 and G2/M phases through p53-dependant up-regulation of p21 in human osteosarcoma cells [6] and induction of apoptosis in breast cancer cells [7]. In addition, BBR has an anti-metastatic effect by the modulation of MMP-1, -2, and -9 in breast cancer and gastric cancer cells [8,9,10]. Here, we investigated the effect of BBR on the anti-angiogenic mechanism in breast cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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Berberine Suppresses TPA-Induced Fibronectin Expression through the Inhibition of VEGF Secretion in Breast Cancer Cells

Kim

Lee

et al. 2013

Cell Physiol Biochem

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Background/Aims: Berberine (BBR) is an isoquinoline alkaloid and is beneficial for the anticancer effect on a variety of human tumor cells. However, BBR's anti-angiogenesis property and its clinical potential as an inhibitor of tumor angiogenesis in breast cancer cells have not been fully elucidated. Here, we investigated the effect of BBR on TPA-induced VEGF and fibronectin (FN) as well as VEGF-induced FN in breast cancer cells. Methods: The secretion of VEGF protein was detected by ELISA. Fibronectin mRNA and protein expression was analyzed by Real-Time PCR and western blotting, respectively. The overexpressions of CA-MEK, and CA-Akt were examined by adenovirus system. Results: Our results showed that TPA, a tumor promoter, significantly increased the level of VEGF and FN expression in both MCF7 and T47D breast cancer cells. On the other hand, TPA-induced VEGF and FN expression was suppressed by LY294002, a PI-3K inhibitor. In contrast, the level of FN expression also significantly increased by constitutively active (CA)-AKT overexpression. We also found that TPA-induced VEGF and FN expression was decreased by BBR treatment. Finally, our results showed that VEGF augmented the expression of FN whereas VEGF-induced FN expression was decreased by BBR treatment. Conclusion: Taken together, we suggest that BBR may suppress TPA-induced VEGF and FN as well as VEGF-induced FN through the inhibition of the PI-3K/AKT pathway in breast cancer cells. Therefore, we suggest that BBR may be used as a candidate drug for the inhibition of angiogenesis of human breast cancer.

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Section: Resultssupporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Berberine Suppresses TPA-Induced Fibronectin Expression through the Inhibition of VEGF Secretion in Breast Cancer Cells

Kim

Lee

et al. 2013

Cell Physiol Biochem

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“…Tissue inhibitors of MMP (TIMP3), which is up-regulated after berberine expose in MCF-7 cells, has been recognized as potential inhibitors of angiogenesis and cancer invasion and metastasis (Ahonen et al, 2002). Interestingly, it demonstrated that berberine suppressed the activities of MMP1, MMP2, MMP9 (Sekhon et al, 2008;Kim et al, 2012), therefore, our results suggested that berberine inhibited the activities of MMPs may be via up-regulation of TIMP3 expression. SLC7A11, which mediates cystine -glutamate exchange and thereby regulates intracellular glutathione (GSH) levels, play an important role in maintaining the higher GSH and consequently in cisplatin resistance (Okuno et al, 2003).…”

Section: 6089 Genomic Screening For Targets Regulated By Berberine Imentioning

confidence: 56%

Genomic Screening for Targets Regulated by Berberine in Breast Cancer Cells

Wen¹,

Wu²,

Fu³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Berberine, a common isoquinoline alkaloid, has been shown to possess anti-cancer activities. However, the underlying molecular mechanisms are still not completely understood. In the current study, we investigated the effects of berberine on cell growth, colony formation, cell cycle distribution, and whether it improved the anticancer efficiency of cisplatin and doxorubicin in human breast cancer estrogen receptor positive (ER+) MCF-7 cells and estrogen receptor negative (ER-) MDA-MB-231 cells. Notably, berberine treatment significantly inhibited cell growth and colony formation in the two cell lines, berberine in combination with cisplatin exerting synergistic growth inhibitory effects. Accompanied by decreased growth, berberine induced G1 phase arrest in MCF-7 but not MDA-MB-231 cells. To provide a more detailed understanding of the mechanisms of action of berberine, we performed genome-wide expression profiling of berberine-treated cells using cDNA microarrays. This revealed that there were 3,397 and 2,706 genes regulated by berberine in MCF-7 and MDA-MB-231 cells, respectively. Fene oncology (GO) analysis identified that many of the target genes were involved in regulation of the cell cycle, cell migration, apoptosis, and drug responses. To confirm the microarray data, qPCR analysis was conducted for 10 selected genes based on previously reported associations with breast cancer and GO analysis. In conclusion, berberine exhibits inhibitory effects on breast cancer cells proliferation, which is likely mediated by alteration of gene expression profiles.

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“…In a previous study, we reported that BBR suppresses the invasiveness of breast cancer cells through inhibition of PKC-a [23]. Here, we investigated the effect of BBR on the expression of TGF-β proteins, which are powerful modulators of the EMT in a variety of cancer cells including breast cancer cells.…”

Section: Resultsmentioning

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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Berberine Suppresses the TPA-Induced MMP-1 and MMP-9 Expressions Through the Inhibition of PKC-α in Breast Cancer Cells

Cited by 56 publications

References 33 publications

Berberine Suppresses TPA-Induced Fibronectin Expression through the Inhibition of VEGF Secretion in Breast Cancer Cells

Berberine Suppresses TPA-Induced Fibronectin Expression through the Inhibition of VEGF Secretion in Breast Cancer Cells

Genomic Screening for Targets Regulated by Berberine in Breast Cancer Cells

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

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