Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is pyruvylated during 3-bromopyruvate mediated cancer cell death.
Anticancer Res
; 29(12): 4909-18, 2009 Dec.
Article
em En
| MEDLINE
| ID: mdl-20044597
ABSTRACT
BACKGROUND:
The pyruvic acid analog 3-bromopyruvate (3BrPA) is an alkylating agent known to induce cancer cell death by blocking glycolysis. The anti-glycolytic effect of 3BrPA is considered to be the inactivation of glycolytic enzymes. Yet, there is a lack of experimental documentation on the direct interaction of 3BrPA with any of the suggested targets during its anticancer effect. METHODS ANDRESULTS:
In the current study, using radiolabeled ((14)C) 3BrPA in multiple cancer cell lines, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was identified as the primary intracellular target of 3BrPA, based on two-dimensional (2D) gel electrophoretic autoradiography, mass spectrometry and immunoprecipitation. Furthermore, in vitro enzyme kinetic studies established that 3BrPA has marked affinity to GAPDH. Finally, Annexin V staining and active caspase-3 immunoblotting demonstrated that apoptosis was induced by 3BrPA.CONCLUSION:
GAPDH pyruvylation by 3BrPA affects its enzymatic function and is the primary intracellular target in 3BrPA mediated cancer cell death.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piruvatos
/
Apoptose
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Carcinoma Hepatocelular
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Gliceraldeído-3-Fosfato Desidrogenases
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Neoplasias Hepáticas
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Anticancer Res
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos