Curcumin suppresses the TPA-induced invasion through inhibition of PKCα-dependent MMP-expression in MCF-7 human breast cancer cells.

Abstract

Curcumin (diferuloylmethane) is a polyphenol derived from the plant turmeric (Curcuma longa), which is commonly used as a spice. Although anti-carcinogenic, anti-oxidant, anti-inflammation, and anti-angiogenic properties have been reported, the effect of curcumin on breast cancer metastasis is unknown. Matrix metalloproteinase-9 (MMP-9) is a major component in cancer cell invasion. In this study, we investigated the inhibitory effect of curcumin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion and the molecular mechanisms involved in MCF-7 cells. Our results showed that curcumin inhibits TPA-induced MMP-9 expression and cell invasion through suppressing NF-κB and AP-1 activation. Also, curcumin strongly repressed the TPA-induced phosphorylation of p38 and JNK and inhibited TPA-induced translocation of PKCα from the cytosol to the membrane, but did not affect the translocation of PKCδ. These results indicate that curcumin-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the PKCα, MAPK and NF-κB/AP-1 pathway in MCF-7 cells. Curcumin may have potential value in restricting breast cancer metastasis.

• Authors: Jeong-Mi Kim, Eun-Mi Noh, Kang-Beam Kwon, Jong-Suk Kim, Yong-Ouk You, Jin-Ki Hwang, Bo-Mi Hwang, Byeong-Soo Kim, Sung-Hoo Lee, Seung Jin Lee, Sung Hoo Jung, Hyun Jo Youn, Young-Rae Lee
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 19 Issue 12 Pg. 1085-92 (Sep 15 2012) ISSN: 1618-095X [Electronic] Germany
• PMID: 22921746 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier GmbH. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• NF-kappa B
• Plant Extracts
• Transcription Factor AP-1
• Protein Kinase C-alpha
• JNK Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases
• Matrix Metalloproteinase 9
• Curcumin
• Tetradecanoylphorbol Acetate

Topics

• Antineoplastic Agents, Phytogenic (pharmacology, therapeutic use)
• Biological Transport (drug effects)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Cell Movement (drug effects)
• Curcuma (chemistry)
• Curcumin (pharmacology, therapeutic use)
• Female
• Humans
• JNK Mitogen-Activated Protein Kinases (metabolism)
• MCF-7 Cells
• Matrix Metalloproteinase 9 (metabolism)
• NF-kappa B (metabolism)
• Neoplasm Metastasis (prevention & control)
• Phytotherapy
• Plant Extracts (pharmacology, therapeutic use)
• Protein Kinase C-alpha (metabolism)
• Signal Transduction
• Tetradecanoylphorbol Acetate
• Transcription Factor AP-1 (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)