Celastrol isolated from Tripterygium regelii induces apoptosis through both caspase-dependent and -independent pathways in human breast cancer cells.
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 (1)H NMR and (13)C 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.
Department of Food and Nutrition, Sunchon National University, Suncheon, Republic of Korea.
Hee-Sun
HS
Yang
Jae-Yong
JY
Kim
Ju-Hye
JH
Lee
Byong-Won
BW
Lee
Ki-Hun
KH
Park
Ki-Hwan
KH
Shim
Mi-Kyung
MK
Lee
Kwon-Il
KI
Seo
D000199:Actins / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015394:Molecular Structure; D053978:Pentacyclic Triterpenes; D029757:Tripterygium / Q000737:chemistry*; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*
D000199:Actins; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D051033:Apoptosis Inducing Factor; D061945:Caspase Inhibitors; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D045304:Cytochromes c; D020169:Caspases; C050414:celastrol