title: 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.affiliation: Molecular Cancer Research Center, Yanbian University, Yanji, Jilin 133002, P.R. China.
authors.forename: Chunliu
authors.initials: C
authors.lastname: Mi
authors.affiliation: Molecular Cancer Research Center, Yanbian University, Yanji, Jilin 133002, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Shi
authors.affiliation: 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.
authors.forename: Juan
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Pharmacy, Jilin Province People's Hospital, Changchun, Jilin 130021, P.R. China.
authors.forename: Li Zhuo
authors.initials: LZ
authors.lastname: Han
authors.affiliation: Molecular Cancer Research Center, Yanbian University, Yanji, Jilin 133002, P.R. China.
authors.forename: Jung Joon
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Jin
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms; D002465:Cell Movement; D015536:Down-Regulation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D015870:Gene Expression; D006801:Humans; D061986:MCF-7 Cells; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D053978:Pentacyclic Triterpenes; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C050414:celastrol