부산대학교 도서관

Alantolactone is a sesquiterpene lactone isolatedfrom Inula helenium L. Although alantolactone possessesanti-inflammation and apoptosis-induction activities, theunderlying mechanism of anti-cancer effect on humanbreast cancer cells remains largely unknown. In this study,we explored the possibility of alantolactone as an apoptosis-inducing cytotoxic agent using MDA-MB-231 cells asin vitro model. Alantolactone significantly induced itsapoptosis, demonstrated by cell cycle analysis, annexinV-APC/7-AAD double staining and dUTP nick end labeling. Additionally, alantolactone triggered the mitochondrial-mediated caspase cascade apoptotic pathway, whichwas confirmed by increased Bax/Bcl-2 ratio, loss of MMP,release of cytc from mitochondria to cytoplasm, activationof caspase 9/3, and subsequent cleavage of PARP. Z-VADFMKpartially prevented apoptosis induced by alantolactone. Alantolactone provoked the production of ROS, whileNAC (a scavenger of ROS) reversed alantolactone-mediateddepolarization of MMP and apoptosis. Alantolactonemodulated the activities of MAPKs. As expected, cotreatmentwith SB203580, SP600125 or U0126 could reducedthe apoptotic rate. Furthermore, alantolactone decreasedthe protein expressions of p-NF-kB p65 and p-STAT3,increased p-c-Jun level in a dose-dependent manner. Thesefindings suggested that alantolactone possessed anticanceractivity via ROS-mediated mitochondrial dysfunctioninvolving MAPK pathway, and had an effect on the transcriptionfactors of NF-kB, AP-1 and STAT3.