Apoptotic potential of sesquiterpene lactone ergolide through the inhibition of NF-kappaB signaling pathway.

Abstract

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.

• Authors: Yong Jin Song, Dae Young Lee, Su-Nam Kim, Kang Ro Lee, Hyang Woo Lee, Jeung-Whan Han, Dong-Won Kang, Hoi Young Lee, Yong Kee Kim
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 57 Issue 12 Pg. 1591-7 (Dec 2005) ISSN: 0022-3573 [Print] England
• PMID: 16354403 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lactones
• NF-kappa B
• Sesquiterpenes
• ergolide
• Luciferases

Topics

• Apoptosis (drug effects)
• Genes, Reporter
• HeLa Cells
• Humans
• Jurkat Cells
• Lactones (pharmacology)
• Luciferases (genetics)
• NF-kappa B (antagonists & inhibitors, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Sesquiterpenes (pharmacology)
• Signal Transduction (drug effects)