Berberine suppresses the TPA-induced MMP-1 and MMP-9 expressions through the inhibition of PKC-α in breast cancer cells

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
JournalJournal of Surgical Research
Volume176
Issue number1
DOIs
Publication statusPublished - 2012 Jul 1
Externally publishedYes

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Berberine
Matrix Metalloproteinases
Breast Neoplasms
Messenger RNA
Phosphorylation
Small Interfering RNA
Cell Cycle
Proteins
Neoplasm Metastasis

Keywords

  • berberine
  • MMP-1
  • MMP-9
  • PKC-α

ASJC Scopus subject areas

  • Surgery

Cite this

Berberine suppresses the TPA-induced MMP-1 and MMP-9 expressions through the inhibition of PKC-α in breast cancer cells. / 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; Nam, Seok Jin.

In: Journal of Surgical Research, Vol. 176, No. 1, 01.07.2012.

Research output: Contribution to journalArticle

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 ; Nam, Seok Jin. / Berberine suppresses the TPA-induced MMP-1 and MMP-9 expressions through the inhibition of PKC-α in breast cancer cells. In: Journal of Surgical Research. 2012 ; Vol. 176, No. 1.
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T1 - Berberine suppresses the TPA-induced MMP-1 and MMP-9 expressions through the inhibition of PKC-α in breast cancer cells

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AU - Han, Jeonghun

AU - Lee, Se Kyung

AU - Choi, Min Young

AU - Kim, Jiyoung

AU - Lee, Jeonghui

AU - Jung, Seung Pil

AU - Kim, Jee Soo

AU - Kim, Jung Han

AU - Choe, Jun Ho

AU - Lee, Jeong Eon

AU - Nam, Seok Jin

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AB - 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.

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