title: Epigenetic reactivation of RANK in glioblastoma cells by curcumin: involvement of STAT3 inhibition.
abstract: 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.
authors.affiliation: Affiliated Bayi Brain Hospital, Bayi Clinical College, Southern Medical University, Beijing, People's Republic of China.
authors.forename: Bingshan
authors.initials: B
authors.lastname: Wu
authors.forename: Xueqin
authors.initials: X
authors.lastname: Yao
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Nie
authors.forename: Ruxiang
authors.initials: R
authors.lastname: Xu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018899:CpG Islands; D003474:Curcumin / Q000494:pharmacology*; D019175:DNA Methylation / Q000187:drug effects; D015257:DNA-Cytosine Methylases / Q000037:antagonists & inhibitors; D044127:Epigenesis, Genetic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D011401:Promoter Regions, Genetic; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D053246:Receptor Activator of Nuclear Factor-kappa B; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C505686:TNFRSF11A protein, human; C081573:DNA modification methylase SssI; D015257:DNA-Cytosine Methylases; D003474:Curcumin