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.
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This work was supported by grants from the National Natural Science Foundation of China (No. 81273532).
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Liu, S., Wu, D., Li, L. et al. 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. Arch. Pharm. Res. 37, 1039–1052 (2014). https://doi.org/10.1007/s12272-013-0270-8
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DOI: https://doi.org/10.1007/s12272-013-0270-8