Deacetylisovaltratum disrupts microtubule dynamics and causes G2/M-phase arrest in human gastric cancer cells in vitro

被引:9
|
作者
Zhang, Dan [1 ,2 ,3 ,4 ]
Zhang, Bo [1 ,2 ,4 ]
Zhou, Li-xin [5 ]
Zhao, Jun [3 ]
Yan, You-you [1 ,2 ]
Li, Yang-ling [1 ,2 ,4 ]
Zeng, Jian-mei [6 ]
Wang, Lin-ling [6 ]
Yang, Bo [6 ]
Lin, Neng-ming [1 ,2 ,4 ,6 ]
机构
[1] Nanjing Med Univ, Hangzhou Peoples Hosp 1, Lab Clin Pharmacol, Hangzhou 310006, Zhejiang, Peoples R China
[2] Hangzhou First Peoples Hosp, Hangzhou Translat Med Res Ctr, Hangzhou 310006, Zhejiang, Peoples R China
[3] Hangzhou Geriatr Hosp, Dept Pharm, Hangzhou 310022, Zhejiang, Peoples R China
[4] Hangzhou First Peoples Hosp, Dept Clin Pharm, Hangzhou 310006, Zhejiang, Peoples R China
[5] Hangzhou First Peoples Hosp, Dept Hepatopancreatobiliary Surg, Hangzhou 310006, Zhejiang, Peoples R China
[6] Zhejiang Chinese Med Univ, Coll Pharmaceut Sci, Hangzhou 310053, Zhejiang, Peoples R China
关键词
deacetylisovaltratum; gastric cancer; cell cycle arrest; microtubules; mitochondrial membrane potential; apoptosis; PATRINIA-HETEROPHYLLA BUNGE; CYCLE ARREST; COLON-CANCER; DNA-DAMAGE; APOPTOSIS; INDUCTION; INHIBITION; PROLIFERATION; CHEMOTHERAPY; MECHANISMS;
D O I
10.1038/aps.2016.91
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Aim: Deacetylisovaltratum (DI) is isolated from the traditional Chinese herbal medicine Patrinia heterophylla Bunge, which exhibits anti-cancer activity. Here, we investigated the effects of DI on human gastric carcinoma cell lines in vitro and elucidated its anti-cancer mechanisms. Methods: Human gastric carcinoma AGS and HGC-27 cell lines were treated with DI, and cell viability was detected with MTT assay. Cell cycle stages, apoptosis and mitochondrial membrane potential were measured using flow cytometry. Protein levels were analyzed by Western blotting. Tubulin polymerization assays and immunofluorescence were used to characterize the tubulin polymerization process. Results: DI inhibited the cell viability of AGS and HGC-27 cells in a dose-and time-dependent manner with IC50 values of 12.0 and 28.8 mu mol/L, respectively, at 24 h of treatment. Treatment with DI (10-100 mu mol/L) dose-dependently promoted tubulin polymerization, and induced significant G(2)/M cell cycle arrest in AGS and HGC-27 cells. Moreover, DI treatment disrupted mitochondrial membrane potential and induced caspase-dependent apoptosis in AGS and HGC-27 cells. Conclusion: DI induces G(2)/M-phase arrest by disrupting tubulin polymerization in human gastric cancer cells, which highlights its potent anti-cancer activity and potential application in gastric cancer therapy.
引用
收藏
页码:1597 / 1605
页数:9
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