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

Mi,Chunliu; Shi,Hui; Ma,Juan; Han,Li  Zhuo; Lee,Jung  Joon; Jin,Xuejun

doi:10.3892/or.2014.3535

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

Authors:
- Chunliu Mi
- Hui Shi
- Juan Ma
- Li Zhuo Han
- Jung Joon Lee
- Xuejun Jin
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Affiliations: Molecular Cancer Research Center, Yanbian University, Yanji, Jilin 133002, P.R. China, Key Laboratory of Natural Resources of Changbai Mountain and Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin 133002, P.R. China, Department of Pharmacy, Jilin Province People's Hospital, Changchun, Jilin 130021, P.R. China
Published online on: October 10, 2014 https://doi.org/10.3892/or.2014.3535
Pages: 2527-2532

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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.

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