Isothiocyanate sulforaphane inhibits protooncogenic ornithine decarboxylase activity in colorectal cancer cells via induction of the TGF-ß/Smad signaling pathway.
Mol Nutr Food Res
; 54(10): 1486-96, 2010 Oct.
Article
en En
| MEDLINE
| ID: mdl-20603835
SCOPE: The objective of this study was to elucidate molecular mechanisms behind the antitumor activities of the isothiocyanate sulforaphane (SFN) in colorectal cancer cells. METHODS AND RESULTS: Cell growth was determined by BrdU incorporation and crystal violet staining. Protein levels were examined by Western blot analysis. Ornithine decarboxylase (ODC) activity was assayed radiometrically. Reverse transcriptase-PCR was used for measuring mRNA expression. For reporter gene assays plasmids were transfected into cells via lipofection and luciferase activity was measured luminometrically. Acetyl-histone H3 and H4 chromatin immunoprecipitation (ChIP) assays were performed followed by PCR with TGF-ß-receptor II promoter specific primers. We could show that SFN-mediated cell growth inhibition closely correlates with a dose-dependent reduction of protein expression and enzymatic activity of ODC. This effect seems to be due to reduced protein levels and transactivation activity of transcription factor c-myc, a direct regulator of ODC expression, as a consequence of SFN-induced TGF-ß/Smad signaling. The coherency of these results was further confirmed by using TGF-ß receptor kinase inhibitor SB431542, which largely abolishes inhibitory effects of SFN on both, ODC activity and cell growth. CONCLUSION: Since elevated ODC enzyme activity is associated with enhanced tumor development, SFN may be a dietary phytochemical with potential to prevent carcinogenesis.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ornitina Descarboxilasa
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Tiocianatos
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Neoplasias Colorrectales
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Transducción de Señal
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Factor de Crecimiento Transformador beta
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Isotiocianatos
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Proteínas Smad
Límite:
Humans
Idioma:
En
Revista:
Mol Nutr Food Res
Asunto de la revista:
CIENCIAS DA NUTRICAO
Año:
2010
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Alemania