Low Nanomolar Cucurbitacin-I Induces G2 / M Phase Arrest and Apoptosis in Gastric Cancer Cells and the Underlying Mechanism
10.3969/j.issn.1008-7125.2017.09.003
- VernacularTitle:低浓度葫芦素-I诱导胃癌细胞G2/M期阻滞和细胞凋亡及其机制研究
- Author:
Jian LI
;
Xiuling XIAO
;
Yan LI
;
Xiaoping ZOU
;
Chao DENG
- Keywords:
Cucurbitacins;
STAT3 Transcription Factor;
Growth Arrest and DNA Damage-Inducible Protein 45alpha;
Mitogen-Activated Protein Kinases;
Stomach Neoplasms;
Cell Cycle;
Apoptosis
- From:Chinese Journal of Gastroenterology
2017;22(9):523-528
- CountryChina
- Language:Chinese
-
Abstract:
Background:Upon inhibition of STAT3 signaling pathway,cucurbitacin-I elicits anticancer effect in various malignancies. However,the anticancer effect and underlying mechanism of cucurbitacin-I in gastric cancer is still elusive. Aims:To explore the effect of low nanomolar cucurbitacin-I on cell proliferation,cell cycle and apoptosis in human gastric cancer cells and the underlying mechanism in vitro. Methods:Human gastric adenocarcinoma cell lines AGS and HGC-27 were treated with cucurbitacin-I at low nanomolar concentration. The anti-proliferative effect of cucurbitacin-I was detected by CCK-8 assay and colony formation assay. Flow cytometry was used to assess the cell cycle and apoptosis. Expressions of cell cycle-related proteins,as well as activation of related pathways such as caspase-3 / PARP apoptotic pathway,STAT3, GADD45α and JNK/ p38 MAPK signaling pathways were determined by Western blotting. Results:Cucurbitacin-I markedly inhibited the growth of gastric cancer cells at low nanomolar concentration by inducing G2 / M phase arrest and apoptosis via a STAT3-independent manner. Furthermore,it was revealed that the anticancer effect of cucurbitacin-I was associated with up-regulation of GADD45α,activation of JNK/ p38 MAPK signaling pathway and the subsequent apoptotic events. Conclusions:The present study provides new insights into the mechanism of anticancer effect of cucurbitacin-I, supporting cucurbitacin-I as an attractive therapeutic drug in gastric cancer.
