title: NF-κB activation was involved in reactive oxygen species-mediated apoptosis and autophagy in 1-oxoeudesm-11(13)-eno-12,8α-lactone-treated human lung cancer cells.
abstract: 1-oxoeudesm-11(13)-eno-12,8α-lactone (OEL), a novel eudesmane-type sesquiterpene compound, has been shown to inhibit the growth of some cancer cell lines and induce significant apoptosis. Here, we investigated the anti-cancer activities of OEL in human lung cancer cells. Our studies demonstrated that OEL induced both apoptosis and autophagy in A549 and H460 cells. OEL-induced autophagy was assessed by appearance of autophagic vacuoles, formation of acidic vesicular organelles, conversion of LC3-I to LC3-II, recruitment of LC3-II to the autophagosomes, and activation of autophagy genes. Furthermore, administration of autophagic inhibitor 3-methyladenine augments OEL-induced apoptotic cell death. The induction of autophagy and apoptosis by OEL links to NF-κB activation and the generation of reactive oxygen species (ROS). Interruption of NF-κB activation by specific inhibitor promotes apoptosis, but decreases autophagy. ROS antioxidants (N-acetylcysteine) attenuated both OEL-induced autophagy and apoptosis. Further experiments confirmed that OEL-induced activation of ROS was increased by NF-κB inhibitor whereas NF-κB activation was not affected by ROS inhibition. These findings suggest that OEL-elicited autophagic response plays a protective role that impedes cell death, and inhibition of autophagy could be an adjunctive strategy for enhancing the chemotherapeutic effect of OEL as an antitumor agent.
authors.affiliation: School of Ocean, Shandong University, Weihai, 264209, People's Republic of China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Liu
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Xiao
authors.initials: X
authors.lastname: Sun
authors.forename: Weidong
authors.initials: W
authors.lastname: Xie
authors.forename: Xia
authors.initials: X
authors.lastname: Li
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D031173:Aster Plant / Q000737:chemistry; D001343:Autophagy / Q000187:drug effects*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D045787:Sesquiterpenes, Eudesmane / Q000494:pharmacology*
chemical_list: C000596332:1-oxoeudesm-11(13)-eno-12,8-lactone; D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D045787:Sesquiterpenes, Eudesmane