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Induction of autophagy by an oleanolic acid derivative, SZC017, promotes ROS‐dependent apoptosis through Akt and JAK2/STAT3 signaling pathway in human lung cancer cells
Author(s) -
Song Yanlin,
Kong Lingqi,
Sun Bin,
Gao Lei,
Chu Peng,
Ahsan Anil,
Qaed Eskandar,
Lin Yuan,
Peng Jinyong,
Ma Xiaodong,
Zhang Jianbin,
Wang Shisheng,
Tang Zeyao
Publication year - 2017
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.10868
Subject(s) - protein kinase b , viability assay , stat3 , a549 cell , autophagy , apoptosis , pi3k/akt/mtor pathway , signal transduction , cancer research , microbiology and biotechnology , chemistry , biology , cancer cell , cancer , biochemistry , genetics
The signal transducers and activators of transcription 3 (STAT3) signaling pathway is a common feature in many solid tumors including non‐small cell lung cancer, whereas current therapies usually fail to treat this disease in majority of cases. In the present study, we aimed to investigate the cytotoxic effect and the underlying mechanisms of SZC017, an oleanolic acid derivative, on human lung cancer cells. Cell viability was significantly decreased in SZC017‐treated lung cancer cells. Mechanistically, SZC017 reduced A549 cell viability by activating both apoptosis and autophagy pathways. SZC017 was able to inhibit the phosphorylation of Akt, JAK2, and STAT3 in A549 cells, resulting in the inactivation of Akt and JAK2/STAT3 signaling pathways. In addition, SZC017 could induce ROS generation and Ca 2+ release. Pretreatment with N‐Acetyl L‐Cysteine, a ROS scavenger, could fully reverse SZC017‐induced ROS and increase the expression of Akt, p‐STAT3, and procaspase‐3, while decrease the ratio of LC3‐II/I and the expression of Beclin‐1. In summary, our study provides pharmacological evidence that SZC017 exhibits potential use in the treatment of lung cancer.