1. Berberine Suppresses the TPA-Induced MMP-1 and MMP-9 Expressions Through the Inhibition of PKC-α in Breast Cancer Cells
- Author
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Kim, Sangmin, Han, Jeonghun, Lee, Se Kyung, Choi, Min-Young, Kim, Jiyoung, Lee, Jeonghui, Jung, Seung Pil, Kim, Jee Soo, Kim, Jung-Han, Choe, Jun-Ho, Lee, Jeong Eon, and Nam, Seok Jin
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BERBERINE , *BREAST cancer treatment , *GENE expression , *PROTEIN kinase C , *WESTERN immunoblotting , *CELL cycle , *MATRIX metalloproteinases - Abstract
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-α phosphorylation were detected by Western blotting. MMP-9 protein expression was detected by gelatin zymography. Cell cycle was analyzed by FACS analysis. PKC-α knock-down was examined by PKC-α 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-α siRNA, respectively. TPA-induced PKC-α phosphorylation was dose-dependently decreased by BBR treatment. Conclusion: The TPA-induced PKC-α 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. [Copyright &y& Elsevier]
- Published
- 2012
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