Celastrol Inhibits Breast Cancer Cell Invasion via Suppression of NF-kappa B-mediated Matrix Metalloproteinase-9 Expression

Abstract

Background/Aims: Metastasis is one of the main causes of death for patients with malignant tumors. Induction of matrix metalloproteinase (MMP)-9 is particularly important for the invasiveness of various cancer cells. Celastrol, a triterpenoid isolated from the traditional Chinese medicine, is known to inhibit the proliferation of a variety of tumor cells, including leukemia, glioma, prostate and breast cancer cells. In this study, we investigated the effect of celastrol on the migration and invasion of human breast carcinoma cells. Results: We observed that celastrol suppressed phorbol 12-myristate 13-acetate (PMA)-induced invasion and migration of MCF-7 cells. We also found that celastrol inhibited PMA-induced MMP-9 expression at both the mRNA and the protein levels, and the proteolytic activity of MMP-9 in MCF-7 cells. Our results revealed that celastrol inhibited the transcriptional activity of MMP-9 by suppression of the DNA binding activity of NF-kappa B in the MMP-9 promoter, and inhibited degradation of I kappa B alpha and nuclear translocation of NF-kappa B. Conclusion: These results indicate that celastrol inhibits NF-kappa B-mediated MMP-9 expression, resulting in suppression of breast cancer cell invasion and migration that is induced by PMA. Celastrol is a potential agent for clinical use in preventing the invasion and metastasis of human malignant breast tumors. Copyright (C) 2011 S. Karger AG, Basel