Celastrol induces the apoptosis of breast cancer cells and inhibits their invasion via downregulation of MMP-9.

Abstract

Celastrol is a quinone methide triterpene derived from Tripterygium wilfordii Hook F., a plant used in traditional medicine. In the present study, we reported that celastrol potentiated tumor necrosis factor-α (TNF-α)-induced apoptosis, affected activation of caspase-8, caspase-3 and PARP cleavage, and inhibited the expression of anti-apoptotic proteins such as cellular inhibitor of apoptosis protein 1 and 2 (cIAP1 and cIAP2), cellular FLICE-inhibitory protein (FLIP), and B-cell lymphoma 2 (Bcl-2). In addition, celastrol significantly reduced the invasion of MDA-MB-231 human breast cancer cells after TNF-α stimulation. As matrix metalloproteinase-9 (MMP-9) plays a critical role in tumor metastasis, we analyzed its expression with celastrol treatment. Western blot analysis and real-time PCR showed that celastrol dose-dependently suppressed TNF-α-induced MMP-9 gene expression at both the mRNA and protein levels in MDA-MB-231 cells. Taken together, our findings indicate that celastrol may be a potential candidate for breast cancer chemotherapy.

• Authors: Chunliu Mi, Hui Shi, Juan Ma, Li Zhuo Han, Jung Joon Lee, Xuejun Jin
• Journal: Oncology reports (Oncol Rep) Vol. 32 Issue 6 Pg. 2527-32 (Dec 2014) ISSN: 1791-2431 [Electronic] Greece
• PMID: 25310109 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Apoptosis Regulatory Proteins
• Pentacyclic Triterpenes
• Triterpenes
• Tumor Necrosis Factor-alpha
• MMP9 protein, human
• Matrix Metalloproteinase 9
• celastrol

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (genetics, metabolism)
• Breast Neoplasms
• Cell Movement
• Down-Regulation (drug effects)
• Drug Screening Assays, Antitumor
• Female
• Gene Expression
• Humans
• MCF-7 Cells
• Matrix Metalloproteinase 9 (genetics, metabolism)
• Neoplasm Invasiveness
• Pentacyclic Triterpenes
• Triterpenes (pharmacology)
• Tumor Necrosis Factor-alpha (pharmacology)