title: Effects of emodin on the demethylation of tumor-suppressor genes in pancreatic cancer PANC-1 cells.
abstract: Emodin, a natural anthraquinone derivative isolated from Rheum palmatum, has been reported to inhibit the growth of pancreatic cancer cells through different modes of action; yet, the detailed mechanism remains unclear. In the present study, we hypothesized that emodin exerts its antitumor effect by participating in the regulation of the DNA methylation level. Our research showed that emodin inhibited the growth of pancreatic cancer PANC-1 cells in a dose- and time-dependent manner. Dot-blot results showed that 40 µM emodin significantly inhibited genomic 5 mC expression in the PANC-1 cells, and mRNA-Seq showed that different concentrations of emodin could alter the gene expression profile in the PANC-1 cells. BSP confirmed that the methylation levels of P16, RASSF1A and ppENK were decreased, while concomitantly the unmethylated status was increased. RT-PCR and western blotting results confirmed that the low expression or absence of expression of mRNA and protein in the PANC-1 cells was re-expressed following treatment with emodin. In conclusion, our study for the first time suggests that emodin inhibits pancreatic cancer cell growth, which may be related to the demethylation of tumor-suppressor genes. The related mechanism may be through the inhibition of methyltransferase expression.
authors.affiliation: Department of Hepatobiliary Surgery, The First Hospital of Jiaxing, Jiaxing, Zhejiang 310012, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, The First Hospital of Jiaxing, Jiaxing, Zhejiang 310012, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Anorectal Surgery, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China.
authors.forename: He-Qi
authors.initials: HQ
authors.lastname: Bu
authors.affiliation: Department of Hepatobiliary Surgery, The First Hospital of Jiaxing, Jiaxing, Zhejiang 310012, P.R. China.
authors.forename: Qing-Jiang
authors.initials: QJ
authors.lastname: Yu
authors.affiliation: Department of Hepatobiliary Surgery, The First Hospital of Jiaxing, Jiaxing, Zhejiang 310012, P.R. China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Jiang
authors.affiliation: Department of Hepatobiliary Surgery, The First Hospital of Jiaxing, Jiaxing, Zhejiang 310012, P.R. China.
authors.forename: Feng-Ping
authors.initials: FP
authors.lastname: Pan
authors.affiliation: Department of Hepatobiliary Surgery, The First Hospital of Jiaxing, Jiaxing, Zhejiang 310012, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Surgery, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Dian-Lei
authors.initials: DL
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary-Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Sheng-Zhang
authors.initials: SZ
authors.lastname: Lin
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019175:DNA Methylation / Q000187:drug effects; D004642:Emodin / Q000008:administration & dosage; D004745:Enkephalins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016328:NF-kappa B / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004745:Enkephalins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D011498:Protein Precursors; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; C033660:preproenkephalin; D004642:Emodin