SP600125 enhances C-2-induced cell death by the switch from autophagy to apoptosis in bladder cancer cells
SP600125 enhances C-2-induced cell death by the switch from autophagy to apoptosis in bladder cancer cells
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SP600125 通过膀胱癌细胞从自噬转变为凋亡来增强 C-2 诱导的细胞死亡
DOI：
10.1186/s13046-019-1467-6
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发表时间：
2019-11
影响因子：
11.3
通讯作者：
Chengyun Jin
中科院分区：
文献类型：
--
作者：
Haiyang Yu;Chunli Wu;Xiangyu Wang;Qianhong Ban;Chunhua Quan;Mengbo Liu;Hangqi Dong;Jinfeng Li;Gi Young Kim;Yung Hyun Choi;Zhenya Wang;Chengyun Jin
BackgroundA natural compound Jaspine B and its derivative possess potential anti-cancer activities; However, little is known about the underlying mechanism. Here, the role of a new autophagy inducer Jaspine B derivative C-2 in suppressing bladder cancer cells was researched in vitro and in vivo.MethodsThe underlying mechanisms and anticancer effect of C-2 in bladder cancer cells were investigated by MTT, western blotting, immunoprecipitation and immunofluorescence assays. The key signaling components were investigated by using pharmacological inhibitors or specific siRNAs. In vivo, we designed a C-2 and SP600125 combination experiment to verify the effectiveness of compound.ResultsC-2 exhibits cytotoxic effect on bladder cancer cells, and JNK activated by C-2 triggers autophagy and up-regulates SQSTM1/p62 proteins, contributing to activation of Nrf2 pathway. Utilization of JNK inhibitor SP600125 or knockdown of JNK by siRNA potentiate the cytotoxicity of C-2 through down-regulation of p62 and LC3II proteins and up-regulation of active-Caspase3 proteins, enhance the cell death effect, facilitating the switch from autophagy to apoptosis. In vivo study, C-2 suppresses tumor growth in a xenograft mouse model of EJ cells without observed toxicity. Combined treatment with SP600125 further enhances tumor inhibition of C-2 associated with enhanced activation of caspase3 and reduction of autophagy.ConclusionsIt reveals a series of molecular mechanisms about SP600125 potentiate the cytotoxicity and tumor inhibition of C-2 in bladder cancer cells through promoting C-2-induced apoptosis, expecting it provides research basis and theoretical support for new drugs development.
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影响因子：
28.5
作者：
Yoshida GJ
通讯作者：
Yoshida GJ
影响因子：
5.3
作者：
通讯作者：
--
影响因子：
29
作者：
Singh R;Cuervo AM
通讯作者：
Cuervo AM
影响因子：
3.5
作者：
Toh PP;Luo S;Menzies FM;Raskó T;Wanker EE;Rubinsztein DC
通讯作者：
Rubinsztein DC
影响因子：
--
作者：
Lee J;Sohn EJ;Yoon S;Won G;Kim CG;Jung JH;Kim SH
通讯作者：
Kim SH