title: 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/G1phase 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.affiliation: Pharmacology Department, Dalian Medical University, 9 West Section, South Road of Lvshun, Dalian, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Sun
authors.affiliation: Pharmacology Department, Dalian Medical University, 9 West Section, South Road of Lvshun, Dalian, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.affiliation: Pharmacology Department, Dalian Medical University, 9 West Section, South Road of Lvshun, Dalian, China.
authors.forename: Anil
authors.initials: A
authors.lastname: Ahsan
authors.affiliation: Pharmacology Department, Dalian Medical University, 9 West Section, South Road of Lvshun, Dalian, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Chu
authors.affiliation: Pharmacology Department, Dalian Medical University, 9 West Section, South Road of Lvshun, Dalian, China.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Song
authors.affiliation: Pharmacology Department, Dalian Medical University, 9 West Section, South Road of Lvshun, Dalian, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Li
authors.affiliation: Pharmacology Department, Dalian Medical University, 9 West Section, South Road of Lvshun, Dalian, China.
authors.forename: Zonghui
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Pharmacology Department, Dalian Medical University, 9 West Section, South Road of Lvshun, Dalian, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Pharmacology Department, Dalian Medical University, 9 West Section, South Road of Lvshun, Dalian, China.
authors.forename: Jinyong
authors.initials: J
authors.lastname: Peng
authors.affiliation: College of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, China.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Song
authors.affiliation: College of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian, China. Electronic address: wangss@dlut.edu.cn.
authors.forename: Shisheng
authors.initials: S
authors.lastname: Wang
authors.affiliation: Pharmacology Department, Dalian Medical University, 9 West Section, South Road of Lvshun, Dalian, China. Electronic address: tangzeyao@aliyun.com.
authors.forename: Zeyao
authors.initials: Z
authors.lastname: Tang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009025:Morpholines / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D051058:Oncogene Protein v-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C000608565:2-morpholinomethyl-3-oxoolean-12-en-28-oic acid; D000970:Antineoplastic Agents; D009025:Morpholines; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D009828:Oleanolic Acid; D051058:Oncogene Protein v-akt
keywords: Akt/NF-κB signaling; Apoptosis; Autophagy; Lung cancer cells; SZC015