NNINspm,naphthalimide-polyamine conjugate,induces hepatoma HepG2 cell apoptosis via PI3K/Akt pathways / 中国药理学通报
Chinese Pharmacological Bulletin
;
(12): 169-174, 2010.
Artigo
em Chinês
| WPRIM
| ID: wpr-403993
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.
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DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Idioma:
Chinês
Revista:
Chinese Pharmacological Bulletin
Ano de publicação:
2010
Tipo de documento:
Artigo
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