Apoptotic potential of sesquiterpene lactone ergolide through the inhibition of NF-kappaB signaling pathway.
Treatment with ergolide, a sesquiterpene lactone from Inula britannica var chinensis, caused the induction of apoptosis in Jurkat T cells, which was confirmed by DNA fragmentation, caspase-3 activation and cleavage of poly(ADP-ribose) polymerase in response to ergolide. Furthermore, mitochondrial dysfunction appeared to be associated with ergolide-induced apoptosis, because Bax translocation and cytochrome c release were stimulated by ergolide. In parallel, the nuclear factor-kappaB (NF-kappaB) signaling pathway was significantly inhibited by ergolide, which was accompanied by down-regulation of cell survival molecules, such as X-chromosome-linked inhibitor of apoptosis and Bcl-2. In addition, the JNK signaling pathway was involved in ergolide-induced apoptosis. Collectively, our results identified a new mechanism for the anti-cancer property of ergolide, attributable to the induction of apoptosis through down-regulation of cell survival signal molecules resulting from inhibition of the NF-kappaB signaling pathway.
Song
Yong Jin
YJ
College of Medicine, Kwandong University, Gangneung 210-701, Korea.
Lee
Dae Young
DY
Kim
Su-Nam
SN
Lee
Kang Ro
KR
Lee
Hyang Woo
HW
Han
Jeung-Whan
JW
Kang
Dong-Won
DW
Lee
Hoi Young
HY
Kim
Yong Kee
YK
D017209:Apoptosis / Q000187:drug effects*; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D007783:Lactones / Q000494:pharmacology*; D008156:Luciferases / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
D007783:Lactones; D016328:NF-kappa B; D012717:Sesquiterpenes; C099797:ergolide; D008156:Luciferases