NNINspm,naphthalimide-polyamine conjugate,induces hepatoma HepG2 cell apoptosis via PI3K/Akt pathways
- VernacularTitle:萘酰亚胺-多胺缀合物NNINspm通过PI_3K/Akt信号通路诱导肝癌细胞凋亡
- Author:
Songqiang XIE
;
Qian LI
;
Yahong ZHANG
;
Jianhong WANG
;
Jin ZHAO
;
Chaojie WANG
- Publication Type:Journal Article
- Keywords:
polyamine conjugate;
polyamine transporter;
cell cycle;
apoptosis;
Akt;
mTOR
- From:
Chinese Pharmacological Bulletin
2010;26(2):169-174
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the apoptotic mechanism and polyamine transporter recognition of 3-nitro-naphthalimide norspermine conjugate (NNINspm),a novel naphthalimide-polyamine conjugate, in HepG2 cells.Methods The cytotoxicity of NNINspm was assessed by MTT assay.Cell cycle distribution and apoptosis were measured by flow cytometry.The protein expression of cytochrome C,14-3-3,Bad,Bcl-xL,mTOR,p70S6K,Cdk4,p27~(kip1),Akt,Caspase-3,Caspase-9 was evaluated by Western blot.The translocation of Akt was detected by high content screening (HCS) analysis.Results NNINspm induced HepG2 cells apoptosis via Akt dephosphorylation and then triggered a series of signal events, such as Bad dephosphorylation, dissociation of 14-3-3 and Bad, and then binding to Bcl-xL,which finally resulted in mitochondrial disruption,cytochrome c release and caspase cascade activation.Furthermore,the NNINspm-mediated cell cycle arrest was due to mTOR and p70S6K dephosphorylation,Cdk4 down-regulation and p27~(kip1) up-regulation.Conclusion NNINspm induces HepG2 cell apoptosis via PI_3K/Akt signal pathway.
