NF-${\kappa}B$ activation was involved in reactive oxygen species-mediated apoptosis and autophagy in 1-oxoeudesm-11(13)-eno-$12,8{\alpha}$-lactone-treated human lung cancer cells

• Published in: Archives of pharmacal research Vol. 37; no. 8; pp. 1039 - 1052
• Main Authors: Liu, Shanshan, Wu, Di, Li, Lin, Sun, Xiao, Xie, Weidong, Li, Xia
• Format: Journal Article
• Language: Korean
• Published: 2014
• Subjects: NF-{\kappa}B; Aster himalaicus; ROS; 1-oxoeudesm-11-eno-$12,8{\alpha}$-lactone; Human lung cancer; Autophagy; Apoptosis
• ISSN: 0253-6269; 1976-3786

1-oxoeudesm-11(13)-eno-$12,8{\alpha}$-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 anticancer 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-${\kappa}B$ activation and the generation of reactive oxygen species (ROS). Interruption of NF-${\kappa}B$ 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-${\kappa}B$ inhibitor whereas NF-${\kappa}B$ 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.