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

Publication date: November 2016
Source:International Immunopharmacology, Volume 40
Author(s): Bin Sun, Lei Gao, Anil Ahsan, Peng Chu, Yanlin Song, Hailong Li, Zonghui Zhang, Yuan Lin, Jinyong Peng, Zhicheng Song, Shisheng Wang, Zeyao Tang
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.

Graphical abstract

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