Sodium butyrate-dependent sensitization of human colon adenocarcinoma COLO 205 cells to TNF-alpha-induced apoptosis.
J Physiol Pharmacol
; 58 Suppl 3: 163-76, 2007 Aug.
Article
en En
| MEDLINE
| ID: mdl-17901592
COLO 205 colon adenocarcinoma cells are highly resistant to extrinsic apoptosis induced by immunomodulatory cytokines. One of the antiapoptotic mechanisms is the expression of cFLIP protein, which inhibits TNF-alpha-induced cell death. The use of metabolic inhibitors, such as sodium butyrate (NaBt), the potent repressor of histone deacetylase, sensitizes tumor cells to TNF-alpha-mediated apoptosis. The Western-blot analysis revealed that in COLO 205 cells the susceptibility to apoptogenic stimuli results from time-dependent reduction in cFLIP(L) protein assembled with DISC complex. At the same time, the level of transmembrane TNF-alpha receptor 1 (TNF-R1) was elevated which is consistent with the exaggerated rate of cell death. Since preincubation of COLO 205 cells with N-acetyl-L-cysteine (NAC), or sodium ascorbate (ASC) did not protect cells from combined NaBt- and TNF-alpha-induced apoptosis, we concluded that deletion of cancer cells is not evoked by oxidative stress. Our results suggest that the combination of TNF-alpha with NaBt targets antiapoptotic protein(s) and may provide efficient and non-toxic treatment of colon cancer.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Butiratos
/
Adenocarcinoma
/
Factor de Necrosis Tumoral alfa
/
Apoptosis
/
Neoplasias del Colon
Límite:
Humans
Idioma:
En
Revista:
J Physiol Pharmacol
Asunto de la revista:
FARMACOLOGIA
/
FISIOLOGIA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Polonia
Pais de publicación:
Polonia