Jaridonin, a new diterpenoid from Isodon rubescens, induces cell cycle arrest in gastric cancer cells through activating ataxia telangiectasia mutated kinase
10.3760/cma.j.issn.0253-3766.2016.04.004
- VernacularTitle:冬凌草中新二萜化合物Jaridonin激活共济失调毛细血管扩张突变蛋白激酶诱导胃癌细胞周期阻滞
- Author:
Yongcheng MA
1
;
Nan SU
;
Ningmin ZHAO
;
Qiaoyan LI
;
Meng ZHANG
;
Hongwei ZHAO
;
Hongmin LIU
;
Yuhua QIN
Author Information
1. 450003,郑州大学人民医院药学部临床药理室
- Keywords:
Stomach neoplasms;
Cell cycle;
Isodon rubescens;
Ent-kaurene diterpenoid;
Antineoplastic agents;
Ataxia-telangiectasia mutated
- From:
Chinese Journal of Oncology
2016;38(4):258-262
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the effects of Jaridonin, a novel diterpenoid from isodon rubescens, on the cell cycle of human gastric cancer cells and its molecular mechanism of action. Methods Flow cytometry was used to analyze the cell cycle distribution and expression of ataxia telangiectasia mutated kinase ( ATM) after Jaridonin treatment. Western blot was performed to detect the expression of cell cycle?related proteins. Results The results of flow cytometry showed that the percentages of MGC?803 cells in G2/M phase at 6 hours after 0, 10, 20 μmol/L Jaridonin?treatment were (10.8±2.2)%, (18.2±2.5)%, (27.3±3.2)%, respectively;those at 12 hours after Jaridonin?treatment were (12.0±1.5)%, (24.1±2.0)%and (39.7±5.2)%, respectively, indicating a G2/M phase arrest of MGC?803 cells was resulted in a time?and dose?dependent manner. The expressions of ATM, Chk1, Chk2, phosphorylated Cdc2 and CDK2 were up?regulated in the MGC?803 cells after Jaridonin treatment, while the levels of Cdc2 and CDK2 were decreased. KU?55933, an inhibitor of ATM, reversed the expression of relevant proteins and G2/M phase arrest induced by Jaridonin. Conclusions Jaridonin can significantly induce G2/M arrest in gastric cancer MGC?803 cells. Its mechanism may be related to the activation of ATM and Chk1/2, and inactivation of Cdc2 and CDK2 phosphorylation.
