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

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• 作者：Sangmin Kim ; Ph.D. ; Jeonghun Han ; M.S. ; Se Kyung Lee ; M.D. ; Min-Young Choi ; M.D. ; Jiyoung Kim ; M.D. ; Jeonghui Lee ; M.D. ; Seung Pil Jung ; M.D. ; Jee Soo Kim ; M.D. ; Jung-Han Kim ; M.D. ; Jun-Ho Choe ; M.D. ; Jeong Eon Lee ; M.D. ; Ph.D. ; ^{paojlus@hanmail.net} ; Seok Jin Nam ; M.D. ; Ph.D. ; ^{sjnam@skku.edu}
• 关键词：berberine ; PKC-¦Á ; MMP-1 ; MMP-9
• 刊名：Journal of Surgical Research
• 出版年：2012
• 出版时间：July, 2012
• 年：2012
• 卷：176
• 期：1
• 页码：e21-e29
• 全文大小：671 K

文摘

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Background

Berberine (BBR) is one of the major alkaloids, and it has been reported to have a variety of pharmacologic effects, including inhibition of cell cycle progression. Here, we investigated the effect of BBR on the MMP-1 and MMP-9 expressions, which are predictors of metastasis and invasion in breast cancer cells.

Methods

MMP-1 and MMP-9 mRNA expressions were analyzed by real-time PCR. The levels of MMP-1 protein and PKC-¦Á phosphorylation were detected by Western blotting. MMP-9 protein expression was detected by gelatin zymography. Cell cycle was analyzed by FACS analysis. PKC-¦Á knock-down was examined by PKC-¦Á siRNA transfection.

Results

The basal levels of both the MMP-1 and MMP-9 mRNA expressions were decreased by BBR treatment in a dose-dependent manner. In contrast, TPA, which is a tumor promoter, significantly increased the levels of the MMP-1 and MMP-9 mRNA and protein expressions in the MCF-7 breast cancer cells. We also observed that the TPA-induced MMP-1 and MMP-9 mRNA and protein expressions were prevented by BBR treatment. In addition, the TPA-induced MMP-1 and MMP-9 expressions were completely decreased by Go6983 and PKC-¦Á siRNA, respectively. TPA-induced PKC-¦Á phosphorylation was dose-dependently decreased by BBR treatment.

Conclusion

The TPA-induced PKC-¦Á phosphorylation is suppressed and then the MMP-1 and MMP-9 expressions are also inhibited by berberine. Therefore, we suggest that berberine may be used as a candidate drug for the inhibition of metastasis of human breast?cancer.