Induction of apoptosis by phenethyl isothiocyanate in cells overexpressing Bcl-XL.
Cancer Lett
; 271(2): 215-21, 2008 Nov 28.
Article
en En
| MEDLINE
| ID: mdl-18639976
ABSTRACT
Isothiocyanates are a class of phytochemicals able to induce apoptosis in numerous cells including Jurkat T-lymphoma cells overexpressing the oncoprotein Bcl-2. To test if isothiocyanates are also effective against other anti-apoptotic members of the Bcl-2 family we generated Jurkat cells stably overexpressing Bcl-X(L). Phenethyl isothiocyanate (PEITC) was cytotoxic to these cells, with an LD(50) ranging from 9 to 18 microM depending on the level of Bcl-X(L) expression. Apoptosis induction in response to PEITC was confirmed by caspase activation and phosphatidylserine exposure. Isothiocyanates specifically target cysteine residues, therefore we tested the hypothesis that PEITC directly impairs Bcl-2 and Bcl-X(L) activity by interacting with their conserved cysteine residues. Jurkat cells overexpressing double cysteine mutants of Bcl-2 were generated, but they remained sensitive to PEITC. We conclude that PEITC antagonizes the action of anti-apoptotic Bcl-2 family members via an indirect mechanism.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Anticarcinógenos
/
Apoptosis
/
Isotiocianatos
/
Proteína bcl-X
Límite:
Humans
Idioma:
En
Revista:
Cancer Lett
Año:
2008
Tipo del documento:
Article
País de afiliación:
Nueva Zelanda