Anticancer effect of SZC015 on lung cancer cells through ROS-dependent apoptosis and autophagy induction mechanisms in vitro.

Abstract

Oleanolic acid (OA) and its several derivatives possess various pharmacological activities, such as antitumor and anti-inflammation. In present study, anticancer effect of SZC015, an OA derivative, and its underlying mechanisms were investigated. We demonstrated that cell viability was significantly decreased in SZC015-treated lung cancer cells, but has less cytotoxicity in human bronchial epithelial cell line. Further investigation verified that apoptosis and autophagy induction and G0/G1 phase arrest were observed in SZC015-treated H322 cells. Mechanically, the level of Akt, p-Akt, p-IκBα, and total p65, the p-p65 in the cytoplasm and nucleus were suppressed by SZC015 in H322 cells, respectively. Inhibition of p65 nuclear translocation was also confirmed by immunofluorescence staining. In addition, co-treatment with chloroquine, an autophagy inhibitor, significantly inhibited SZC015-induced autophagy and enhanced SZC015-induced apoptotic cell death. Intracellular ROS was increased in a concentration-dependent manner, which could be prevented by N-Acetyl l-Cysteine, an ROS scavenger. Moreover, the level of Akt and procaspase-3 were increased, while the ratio of LC3 II/I was decreased. Taken together, our study demonstrates that the inhibitory effect of SZC015 against H322 cells is mediated by excessive ROS generation that could suppress Akt/NF-κB signaling pathway, which thereby leads to apoptotic and autophagic cell death.

• Authors: Bin Sun, Lei Gao, Anil Ahsan, Peng Chu, Yanlin Song, Hailong Li, Zonghui Zhang, Yuan Lin, Jinyong Peng, Zhicheng Song, Shisheng Wang, Zeyao Tang
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 40 Pg. 400-409 (Nov 2016) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 27697723 (Publication Type: Journal Article)
• Copyright: Copyright © 2016. Published by Elsevier B.V.

Chemical References

• 2-morpholinomethyl-3-oxoolean-12-en-28-oic acid
• Antineoplastic Agents
• Morpholines
• NF-kappa B
• Reactive Oxygen Species
• Oleanolic Acid
• Oncogene Protein v-akt

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Humans
• Lung Neoplasms (drug therapy, pathology)
• Morpholines (pharmacology)
• NF-kappa B (metabolism)
• Oleanolic Acid (analogs & derivatives, pharmacology)
• Oncogene Protein v-akt (metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)