Celastrol isolated from Tripterygium regelii induces apoptosis through both caspase-dependent and -independent pathways in human breast cancer cells

• Published in: Food and chemical toxicology 2011-02, Vol.49 (2), p.527-532
• Main Authors: Yang, Hee-Sun, Kim, Jae-Yong, Lee, Ju-Hye, Lee, Byong-Won, Park, Ki-Hun, Shim, Ki-Hwan, Lee, Mi-Kyung, Seo, Kwon-Il
• Format: Article
• Language: English
• Subjects: Actins - metabolism; adenocarcinoma; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Apoptosis - drug effects; Apoptosis Inducing Factor - genetics; Apoptosis Inducing Factor - metabolism; Biological and medical sciences; breast neoplasms; Breast Neoplasms - drug therapy; Caspase Inhibitors; caspase-7; Caspases - metabolism; Celastrol; cell growth; Cell Line, Tumor; chemical structure; chloroform; chromatography; condensation; cytochrome c; Cytochromes c - genetics; Cytochromes c - metabolism; DNA; Dose-Response Relationship, Drug; Female; Gene Expression Regulation, Neoplastic; General pharmacology; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; MCF-7; Medical sciences; Molecular Structure; neoplasm cells; nuclear magnetic resonance spectroscopy; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; silica gel; toxicology; Tripterygium; Tripterygium - chemistry; Tripterygium regelii; Triterpenes - chemistry; Triterpenes - pharmacology; Tumors
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2010.11.044

The aim of the present study was to evaluate the underlying apoptotic mechanisms of celastrol, a major biologically active component of Tripterygium regelii, in human breast adenocarcinoma MCF-7 cells. Celastrol was isolated from T. regelii chloroform extract by silica gel column chromatography, and its chemical structure was identified via 1H NMR and 13C NMR. Celastrol significantly inhibited cell growth in dose- and time-dependent manners. Celastrol induced sub-G1 DNA accumulation, formation of apoptotic bodies, nuclear condensation, and a DNA ladder in MCF-7 cells. Celastrol triggered the activation of caspase family proteins. Celastrol caused activation of caspase-7, -8, and -9, PARP cleavage, caspase-8-mediated bid cleavage, and release of cytochrome c and AIF. In addition, celastrol decreased the expression of anti-apoptotic Bcl-2 protein and increased expression of pro-apoptotic Bax protein. These results suggest that celastrol inhibits the proliferation of MCF-7 cells through induction of apoptosis, which is mediated by a mitochondrial-dependent caspase pathway.