Epigenetic reactivation of RANK in glioblastoma cells by curcumin: involvement of STAT3 inhibition.
DNA Cell Biol
; 32(6): 292-7, 2013 Jun.
Article
en En
| MEDLINE
| ID: mdl-23621850
DNA methylation plays an essential role in carcinogenesis. Promoter hypermethylation can result in transcriptional silencing of specific genes, such as tumor suppressors. Thus far, few reports have investigated the effect of curcumin, an active component of the perennial herb Curcuma longa, on DNA methylation. In the present study, we evaluated the effects of curcumin on receptor activator of NF-κB (RANK) gene expression in human glioblastoma cells. Incubation of cells with therapeutic concentrations of curcumin resulted in a significant elevation of RANK expression at both the mRNA and protein levels in two glioblastoma cell lines. We further confirmed that this elevation was associated with promoter demethylation through methylation-specific polymerase chain reaction (PCR) and bisulfite sequencing PCR. Additionally, we demonstrated that knockdown of STAT3, an oncogenic transcription factor, is sufficient to induce RANK promoter demethylation along with RANK reactivation. These results demonstrated that curcumin induced RANK gene reactivation through epigenetic modification in human glioblastoma cells, and that STAT3 is involved in RANK promoter hypermethylation and epigenetic silencing, thus allowing for further applications of curcumin epigenetic therapy in glioma and therapeutic implications of STAT3 in human glioblastoma.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Glioblastoma
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Curcumina
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Factor de Transcripción STAT3
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Receptor Activador del Factor Nuclear kappa-B
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Antineoplásicos Fitogénicos
Límite:
Humans
Idioma:
En
Revista:
DNA Cell Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2013
Tipo del documento:
Article
Pais de publicación:
Estados Unidos