DNMT1 is the maintenance DNA methyltransferase shown to be essential for embryonic development and cellular growth and differentiation in many somatic tissues in mammals. Increasing evidence has also suggested a role for DNMT1 in repressing gene expression through interactions with specific transcription factors. Previously, we identified DNMT1 as an interacting partner of the TR2/TR4 nuclear receptor heterodimer in erythroid cells, implicated in the developmental silencing of fetal β-type globin genes in the adult stage of human erythropoiesis. Here, we extended this work by using a biotinylation tagging approach to characterize DNMT1 protein complexes in mouse erythroleukemic cells. We identified novel DNMT1 interactions with several hematopoietic transcription factors with essential roles in erythroid differentiation, including GATA1, GFI-1b and FOG-1. We provide evidence for DNMT1 forming distinct protein subcomplexes with specific transcription factors and propose the existence of a "core" DNMT1 complex with the transcription factors ZBP-89 and ZNF143, which is also present in non-hematopoietic cells. Furthermore, we identified the short (17a.a.) PCNA Binding Domain (PBD) located near the N-terminus of DNMT1 as being necessary for mediating interactions with the transcription factors described herein. Lastly, we provide evidence for DNMT1 serving as a co-repressor of ZBP-89 and GATA1 acting through upstream regulatory elements of the PU.1 and GATA1 gene loci.

• Klíčová slova
• DNMT1, Epigenetics, Erythropoiesis, Transcription factors,
• MeSH
• buněčná diferenciace genetika   MeSH
• DNA vazebné proteiny genetika   metabolismus   MeSH
• DNA-(cytosin-5-)methyltransferasa genetika   metabolismus   MeSH
• DNA-(cytosin-5)-methyltransferasa 1 MeSH
• erytroidní buňky chemie   metabolismus   MeSH
• jaderné proteiny genetika   metabolismus   MeSH
• lidé MeSH
• metylace DNA genetika   MeSH
• multiproteinové komplexy genetika   metabolismus   MeSH
• myši MeSH
• protoonkogenní proteiny genetika   metabolismus   MeSH
• regulace genové exprese genetika   MeSH
• represorové proteiny genetika   metabolismus   MeSH
• trans-aktivátory genetika   metabolismus   MeSH
• transkripční faktor GATA1 genetika   metabolismus   MeSH
• transkripční faktory genetika   metabolismus   MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• DNA vazebné proteiny MeSH
• DNA-(cytosin-5-)methyltransferasa MeSH
• DNA-(cytosin-5)-methyltransferasa 1 MeSH
• DNMT1 protein, human MeSH Prohlížeč
• Dnmt1 protein, mouse MeSH Prohlížeč
• Gata1 protein, mouse MeSH Prohlížeč
• Gfi1b protein, mouse MeSH Prohlížeč
• jaderné proteiny MeSH
• multiproteinové komplexy MeSH
• proto-oncogene protein Spi-1 MeSH Prohlížeč
• protoonkogenní proteiny MeSH
• represorové proteiny MeSH
• trans-aktivátory MeSH
• transkripční faktor GATA1 MeSH
• transkripční faktory MeSH
• Zfp148 protein, mouse MeSH Prohlížeč
• Zfpm1 protein, mouse MeSH Prohlížeč

The fusion of sperm and oocytes determines the fertilization competence and subsequent development of embryos, which, in turn, can be affected by various proteins and DNA methylation. However, several factors in this whole regulation process remain unknown, especially in yaks. Here, we report that fibroblast growth factor 10 (FGF10) is an important growth factor that can enhance the maturation rate of yak oocytes and the motility of frozen spermatozoa. Subsequent blastocyst quality was also improved by increasing the total cell number and level of pregnancy-associated protein in blastocysts. These effects were significantly high in the group that received the 5 ng/ml FGF10 treatment, during both in vitro maturation (IVM) and capacitation. Our data show that the effects of FGF10 were dose-dependent at vital steps of embryogenesis in vitro. Furthermore, quantitative polymerase chain reaction, western blot analysis, and immunofluorescence demonstrated that the levels of CD9, CD81, DNMT1, and DNMT3B in both mature cumulus-oocyte complexes and capacitated sperms were regulated by FGF10, which was also highly expressed in the group treated with 5 ng/ml FGF10 during both IVM and capacitation. From our present study, we concluded that FGF10 promotes yak oocyte fertilization competence and subsequent blastocyst quality, and could also regulate CD9, CD81, DNMT1, and DNMT3B to optimize sperm-oocyte interactions and DNA methylation during fertilization.

• Klíčová slova
• DNA methylation, embryonic development, fertilization, fibroblast growth factors (FGFs), sperm-oocyte fusion, yak,
• MeSH
• antigeny CD81 genetika   metabolismus   MeSH
• antigeny CD9 genetika   metabolismus   MeSH
• blastocysta účinky léků   fyziologie   MeSH
• DNA-(cytosin-5-)methyltransferasa genetika   metabolismus   MeSH
• DNA-(cytosin-5)-methyltransferasa 1 genetika   metabolismus   MeSH
• DNA-methyltransferasa 3B MeSH
• embryonální vývoj účinky léků   genetika   fyziologie   MeSH
• fertilizace in vitro veterinární   MeSH
• fertilizace účinky léků   genetika   fyziologie   MeSH
• fibroblastový růstový faktor 10 aplikace a dávkování   fyziologie   MeSH
• IVM techniky veterinární   MeSH
• messenger RNA genetika   metabolismus   MeSH
• oocyty účinky léků   fyziologie   MeSH
• skot embryologie   genetika   fyziologie   MeSH
• těhotenství MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• skot embryologie   genetika   fyziologie   MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD81 MeSH
• antigeny CD9 MeSH
• DNA-(cytosin-5-)methyltransferasa MeSH
• DNA-(cytosin-5)-methyltransferasa 1 MeSH
• fibroblastový růstový faktor 10 MeSH
• messenger RNA MeSH

Adiposis is reputed as a twin disease of type 2 diabetes and greatly harmful to human health. In order to understand the molecular mechanisms of adiposis, the changes of physiological, pathological, epigenetic and correlative gene expression were investigated during the adiposis development of C57BL/6J mice induced by long time (9 months) high-fat and high-sucrose diet (HFSD) sustainably. The results showed that mRNA transcription level of the Leptin, Glut4 and Glut2 genes have been obviously changed, which exhibit a negative correlation with methylation on their promoter DNA. The results also revealed that HFSD induced higher level of DNA methyltransferase 1 (DNMT1) in fat tissue might play important role in regulating the changes of methylation pattern on Glut4 and Leptin genes, and which might be one of the molecular mechanisms for the adiposis development.

• MeSH
• adipozita fyziologie   MeSH
• časové faktory MeSH
• dieta s vysokým obsahem tuků škodlivé účinky   trendy   MeSH
• DNA-(cytosin-5)-methyltransferasa 1 metabolismus   MeSH
• játra metabolismus   patologie   MeSH
• konzumní sacharóza škodlivé účinky   MeSH
• leptin metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• přenašeč glukosy typ 4 metabolismus   MeSH
• tuková tkáň metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA-(cytosin-5)-methyltransferasa 1 MeSH
• Dnmt1 protein, mouse MeSH Prohlížeč
• konzumní sacharóza MeSH
• leptin MeSH
• přenašeč glukosy typ 4 MeSH
• Slc2a4 protein, mouse MeSH Prohlížeč

GATA-1 and PU.1 are two important hematopoietic transcription factors that mutually inhibit each other in progenitor cells to guide entrance into the erythroid or myeloid lineage, respectively. PU.1 controls its own expression during myelopoiesis by binding to the distal URE enhancer, whose deletion leads to acute myeloid leukemia (AML). We herein present evidence that GATA-1 binds to the PU.1 gene and inhibits its expression in human AML-erythroleukemias (EL). Furthermore, GATA-1 together with DNA methyl Transferase I (DNMT1) mediate repression of the PU.1 gene through the URE. Repression of the PU.1 gene involves both DNA methylation at the URE and its histone H3 lysine-K9 methylation and deacetylation as well as the H3K27 methylation at additional DNA elements and the promoter. The GATA-1-mediated inhibition of PU.1 gene transcription in human AML-EL mediated through the URE represents important mechanism that contributes to PU.1 downregulation and leukemogenesis that is sensitive to DNA demethylation therapy.

• MeSH
• akutní erytroblastická leukemie genetika   patologie   MeSH
• akutní myeloidní leukemie genetika   patologie   MeSH
• buněčná diferenciace genetika   MeSH
• DNA-(cytosin-5-)methyltransferasa genetika   metabolismus   MeSH
• DNA-(cytosin-5)-methyltransferasa 1 MeSH
• genetická transkripce MeSH
• histony genetika   MeSH
• lidé MeSH
• metylace DNA genetika   MeSH
• promotorové oblasti (genetika) MeSH
• protoonkogenní proteiny biosyntéza   genetika   metabolismus   MeSH
• regulace genové exprese u leukemie MeSH
• trans-aktivátory biosyntéza   genetika   metabolismus   MeSH
• transkripční faktor GATA1 genetika   metabolismus   MeSH
• vazba proteinů MeSH
• zesilovače transkripce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA-(cytosin-5-)methyltransferasa MeSH
• DNA-(cytosin-5)-methyltransferasa 1 MeSH
• DNMT1 protein, human MeSH Prohlížeč
• GATA1 protein, human MeSH Prohlížeč
• histony MeSH
• proto-oncogene protein Spi-1 MeSH Prohlížeč
• protoonkogenní proteiny MeSH
• trans-aktivátory MeSH
• transkripční faktor GATA1 MeSH

Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative disorder of early childhood characterized by mutations activating RAS signaling. Established clinical and genetic markers fail to fully recapitulate the clinical and biological heterogeneity of this disease. Here we report DNA methylome analysis and mutation profiling of 167 JMML samples. We identify three JMML subgroups with unique molecular and clinical characteristics. The high methylation group (HM) is characterized by somatic PTPN11 mutations and poor clinical outcome. The low methylation group is enriched for somatic NRAS and CBL mutations, as well as for Noonan patients, and has a good prognosis. The intermediate methylation group (IM) shows enrichment for monosomy 7 and somatic KRAS mutations. Hypermethylation is associated with repressed chromatin, genes regulated by RAS signaling, frequent co-occurrence of RAS pathway mutations and upregulation of DNMT1 and DNMT3B, suggesting a link between activation of the DNA methylation machinery and mutational patterns in JMML.

• MeSH
• biopsie MeSH
• chromatin genetika   metabolismus   MeSH
• dítě MeSH
• DNA-(cytosin-5-)methyltransferasa metabolismus   MeSH
• DNA-(cytosin-5)-methyltransferasa 1 metabolismus   MeSH
• DNA-methyltransferasa 3B MeSH
• epigenomika MeSH
• juvenilní myelomonocytární leukemie genetika   mortalita   patologie   terapie   MeSH
• kojenec MeSH
• lidé MeSH
• metylace DNA * MeSH
• mutace MeSH
• mutační analýza DNA MeSH
• Noonanové syndrom genetika   patologie   MeSH
• předškolní dítě MeSH
• prognóza MeSH
• prospektivní studie MeSH
• protinádorové látky terapeutické užití   MeSH
• protoonkogenní proteiny c-cbl MeSH
• protoonkogenní proteiny p21(ras) genetika   metabolismus   MeSH
• regulace genové exprese u leukemie MeSH
• signální transdukce genetika   MeSH
• transplantace hematopoetických kmenových buněk MeSH
• tyrosinfosfatasa nereceptorového typu 11 genetika   metabolismus   MeSH
• upregulace MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chromatin MeSH
• DNA-(cytosin-5-)methyltransferasa MeSH
• DNA-(cytosin-5)-methyltransferasa 1 MeSH
• DNMT1 protein, human MeSH Prohlížeč
• KRAS protein, human MeSH Prohlížeč
• protinádorové látky MeSH
• protoonkogenní proteiny c-cbl MeSH
• protoonkogenní proteiny p21(ras) MeSH
• PTPN11 protein, human MeSH Prohlížeč
• tyrosinfosfatasa nereceptorového typu 11 MeSH

DNA methylation plays a pivotal role in the etiology of cancer by mediating epigenetic silencing of cancer-related genes. Since the relationship between aberrant DNA methylation and cancer has been understood, there has been an explosion of research at developing anti-cancer therapies that work by inhibiting DNA methylation. From the discovery of first DNA hypomethylating drugs in the 1980s to recently discovered second generation pro-drugs, exceedingly large number of studies have been published that describe the DNA hypomethylation-based anti-neoplastic action of these drugs in various stages of the pre-clinical investigation and advanced stages of clinical development. This review is a comprehensive report of the literature published in past 40 years, on so far discovered nucleosidic DNA methylation inhibitors in chronological order. The review will provide a complete insight to the readers about the mechanisms of action, efficacy to demethylate and re-express various cancer-related genes, anti-tumor activity, cytotoxicity profile, stability, and bioavailability of these drugs. The review further presents the far known mechanisms of primary and secondary resistance to azanucleoside drugs. Finally, the review highlights the ubiquitous role of DNA hypomethylating epi-drugs as chemosensitizers and/or priming agents, and recapitulate the combinatorial cancer preventive effects of these drugs with other epigenetic agents, conventional chemo-drugs, or immunotherapies. This comprehensive review analyzes the beneficial characteristics and drawbacks of nucleosidic DNA methylation inhibitors, which will assist the pre-clinical and clinical researchers in the design of future experiments to improve the therapeutic efficacy of these drugs and circumvent the challenges in the path of successful epigenetic therapy.

• Klíčová slova
• Combinatorial therapy, DNA hypermethylation, DNA methyltransferase inhibitors, Drug resistance, Gene silencing, Nucleoside analogs,
• MeSH
• azacytidin analogy a deriváty   farmakologie   MeSH
• chemorezistence MeSH
• DNA-(cytosin-5)-methyltransferasa 1 antagonisté a inhibitory   MeSH
• lidé MeSH
• metylace DNA účinky léků   MeSH
• nukleosidy farmakologie   MeSH
• objevování léků * MeSH
• protinádorové látky farmakologie   terapeutické užití   MeSH
• thioguanin farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• azacytidin MeSH
• DNA-(cytosin-5)-methyltransferasa 1 MeSH
• guadecitabine MeSH Prohlížeč
• nukleosidy MeSH
• protinádorové látky MeSH
• thioguanin MeSH

Radiation exposure can evoke cellular stress responses. Emerging recognition that long non-coding RNAs (lncRNAs) act as regulators of gene expression has broadened the spectra of molecules controlling the genomic landscape upon alterations in environmental conditions. Knowledge of the mechanisms responding to low dose irradiation (LDR) exposure is very limited yet most likely involve subtle ancillary molecular pathways other than those protecting the cell from direct cellular damage. The discovery that transcription of the lncRNA PARTICLE (promoter of MAT2A- antisense radiation-induced circulating lncRNA; PARTICL) becomes dramatically instigated within a day after LDR exposure introduced a new gene regulator onto the biological landscape. PARTICLE affords an RNA binding platform for genomic silencers such as DNA methyltransferase 1 and histone tri-methyltransferases to reign in the expression of tumor suppressors such as its neighboring MAT2A in cis as well as WWOX in trans. In silico evidence offers scope to speculate that PARTICLE exploits the abundance of Hoogsten bonds that exist throughout mammalian genomes for triplex formation, presumably a vital feature within this RNA silencer. PARTICLE may provide a buffering riboswitch platform for S-adenosylmethionine. The correlation of PARTICLE triplex formation sites within tumor suppressor genes and their abundance throughout the genome at cancer-related hotspots offers an insight into potential avenues worth exploring in future therapeutic endeavors.

• Klíčová slova
• epigenetics, histone, long non-coding RNA, methyltransferase, radiation, triplex,
• MeSH
• dávka záření MeSH
• DNA-(cytosin-5)-methyltransferasa 1 genetika   MeSH
• genom lidský účinky záření   MeSH
• genomika MeSH
• histonmethyltransferasy genetika   MeSH
• lidé MeSH
• methioninadenosyltransferasa genetika   MeSH
• nádorové supresorové proteiny genetika   MeSH
• nádory genetika   radioterapie   MeSH
• oxidoreduktasa obsahující WW doménu genetika   MeSH
• promotorové oblasti (genetika) genetika   MeSH
• radiační expozice škodlivé účinky   MeSH
• regulace genové exprese u nádorů účinky záření   MeSH
• RNA dlouhá nekódující genetika   MeSH
• RNA interference účinky záření   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA-(cytosin-5)-methyltransferasa 1 MeSH
• DNMT1 protein, human MeSH Prohlížeč
• histonmethyltransferasy MeSH
• MAT2A protein, human MeSH Prohlížeč
• methioninadenosyltransferasa MeSH
• nádorové supresorové proteiny MeSH
• oxidoreduktasa obsahující WW doménu MeSH
• RNA dlouhá nekódující MeSH
• WWOX protein, human MeSH Prohlížeč

STUDY OBJECTIVES: To identify rare allelic variants and HLA alleles in narcolepsy patients with hypocretin (orexin, HCRT) deficiency but lacking DQB1*06:02. SETTINGS: China (Peking University People's Hospital), Czech Republic (Charles University), Denmark (Golstrup Hospital), Italy (University of Bologna), Korea (Catholic University), and USA (Stanford University). DESIGN: CSF hypocretin-1, DQB1*06:02, clinical and polysomnographic data were collected in narcolepsy patients (552 with and 144 without cataplexy) from 6 sites. Numbers of cases with and without DQB1*06:02 and low CSF hypocretin-1 were compiled. HLA class I (A, B, C), class II (DRBs, DQA1, DQB1, DPA1, and DPB1), and whole exome sequencing were conducted in 9 DQB1*06:02 negative cases with low CSF hypocretin-1. Sanger sequencing of selected exons in DNMT1, HCRT, and MOG was performed to exclude mutations in known narcolepsy-associated genes. MEASUREMENTS AND RESULTS: Classic narcolepsy markers DQB1*06:02 and low CSF hypocretin-1 were found in 87.4% of cases with cataplexy, and in 20.0% without cataplexy. Nine cases (all with cataplexy) were DQB1*06:02 negative with low CSF hypocretin-1, constituting 1.7% [0.8%-3.4%] of all cases with cataplexy and 1.8% [0.8%-3.4%] of cases with low CSF hypocretin independent of cataplexy across sites. Five HLA negative subjects had severe cataplexy, often occurring without clear triggers. Subjects had diverse ethnic backgrounds and HLA alleles at all loci, suggesting no single secondary HLA association. The rare subtype DPB1*0901, and homologous DPB1*10:01 subtype, were present in 5 subjects, suggesting a secondary association with HLA-DP. Preprohypocretin sequencing revealed no mutations beyond one previously reported in a very early onset case. No new MOG or DNMT1 mutations were found, nor were suspicious or private variants in novel genes identified through exome sequencing. CONCLUSIONS: Hypocretin, MOG, or DNMT1 mutations are exceptional findings in DQB1*06:02 negative cases with hypocretin deficiency. A secondary HLA-DP association may be present in these cases. These represent particularly difficult diagnostic challenges.

• Klíčová slova
• DNMT1, HLA, MHC, MOG, cataplexy, exome sequencing, hypocretin, narcolepsy, orexin,
• MeSH
• alely MeSH
• glykoprotein v myelinu oligodendrocytů genetika   MeSH
• HLA-DQ beta řetězec genetika   MeSH
• internacionalita MeSH
• intracelulární signální peptidy a proteiny mozkomíšní mok   nedostatek   genetika   MeSH
• kataplexie genetika   MeSH
• kohortové studie MeSH
• lidé MeSH
• mutace genetika   MeSH
• mutační analýza DNA MeSH
• narkolepsie genetika   MeSH
• neuropeptidy mozkomíšní mok   nedostatek   genetika   MeSH
• orexiny MeSH
• represorové proteiny genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• DMAP1 protein, human MeSH Prohlížeč
• glykoprotein v myelinu oligodendrocytů MeSH
• HCRT protein, human MeSH Prohlížeč
• HLA-DQ beta řetězec MeSH
• HLA-DQB1 antigen MeSH Prohlížeč
• intracelulární signální peptidy a proteiny MeSH
• MOG protein, human MeSH Prohlížeč
• neuropeptidy MeSH
• orexiny MeSH
• represorové proteiny MeSH

Epigenetic changes are considered to be a frequent event during tumour development. Hypermethylation of promoter CpG islands represents an alternative mechanism for inactivation of tumour suppressor genes, DNA repair genes, cell cycle regulators and transcription factors. The aim of this study was to investigate promoter methylation of specific genes in samples of sinonasal carcinoma by comparison with normal sinonasal tissue. To search for epigenetic events we used methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) to compare the methylation status of 64 tissue samples of sinonasal carcinomas with 19 control samples. We also compared the human papilloma virus (HPV) status with DNA methylation. Using a 20% cut-off for methylation, we observed significantly higher methylation in RASSF1, CDH13, ESR1 and TP73 genes in the sinonasal cancer group compared with the control group. HPV positivity was found in 15/64 (23.4 %) of all samples in the carcinoma group and in no sample in the control group. No correlation was found between DNA methylation and HPV status. In conclusion, our study showed that there are significant differences in promoter methylation in the RASSF1, ESR 1, TP73 and CDH13 genes between sinonasal carcinoma and normal sinonasal tissue, suggesting the importance of epigenetic changes in these genes in carcinogenesis of the sinonasal area. These findings could be used as prognostic factors and may have implications for future individualised therapies based on epigenetic changes.

• MeSH
• aktivace enzymů MeSH
• dlaždicobuněčné karcinomy hlavy a krku MeSH
• DNA-(cytosin-5-)methyltransferasa genetika   metabolismus   MeSH
• DNA-(cytosin-5)-methyltransferasa 1 MeSH
• epigenomika MeSH
• kadheriny genetika   metabolismus   MeSH
• lidé MeSH
• metylace DNA * MeSH
• nádory hlavy a krku diagnóza   genetika   patofyziologie   virologie   MeSH
• Papillomaviridae izolace a purifikace   MeSH
• prognóza MeSH
• promotorové oblasti (genetika) genetika   MeSH
• spinocelulární karcinom diagnóza   genetika   patofyziologie   virologie   MeSH
• tumor supresorové geny * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA-(cytosin-5-)methyltransferasa MeSH
• DNA-(cytosin-5)-methyltransferasa 1 MeSH
• H-cadherin MeSH Prohlížeč
• kadheriny MeSH

Curcumin has been documented to exert anticancer effects by interacting with altered proliferative and apoptotic pathways in cancer models. In this study, we evaluated the potential of curcumin to reverse promoter methylation of the p15 gene in Raji cells and its ability to induce apoptosis and genomic instability. Anti-neoplastic action of curcumin showed an augmentation in reactive oxygen species (ROS) and cell cycle arrest in G1 phase. Subsequently, curcumin- exposed Raji cells showed structural abnormalities in chromosomes. These observations suggest that curcumin also causes ROS-mediated apoptosis and genomic instability. The treatment of Raji cell line with 10 μM curcumin caused hypomethylation of the p15 promoter after six days. Hypomethylation of p15 was further found to be favoured by downregulation of DNA methyltransferase 1 after 10 μM curcumin treatment for six days. Methylation-specific PCR suggested demethylation of the p15 promoter. Demethylation was further validated by DNA sequencing. Reverse-transcription PCR demonstrated that treatment with curcumin (10 μM) for six days led to the up-regulation of p15 and down-regulation of DNA methyltransferase 1. Furthermore, curcumin- mediated reversal of p15 promoter methylation might be potentiated by down-regulation of DNA methyltransferase 1 expression, which was supported by cell cycle analysis. Furthermore, curcumin acts as a double-pronged agent, as it caused apoptosis and promoter hypomethylation in Raji cells.

• MeSH
• akutní lymfatická leukemie patologie   MeSH
• apoptóza účinky léků   MeSH
• buněčný cyklus účinky léků   MeSH
• DNA-(cytosin-5-)methyltransferasa biosyntéza   genetika   MeSH
• DNA-(cytosin-5)-methyltransferasa 1 MeSH
• down regulace účinky léků   MeSH
• enzymová indukce účinky léků   MeSH
• fytogenní protinádorové látky farmakologie   toxicita   MeSH
• inhibitor p15 cyklin-dependentní kinasy biosyntéza   genetika   MeSH
• kurkumin farmakologie   toxicita   MeSH
• lidé MeSH
• metylace DNA účinky léků   MeSH
• nádorové buněčné linie MeSH
• nádorové proteiny biosyntéza   genetika   MeSH
• nestabilita genomu účinky léků   MeSH
• promotorové oblasti (genetika) účinky léků   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• regulace genové exprese u leukemie účinky léků   MeSH
• screeningové testy protinádorových léčiv MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zlomy chromozomů účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CDKN2B protein, human MeSH Prohlížeč
• DNA-(cytosin-5-)methyltransferasa MeSH
• DNA-(cytosin-5)-methyltransferasa 1 MeSH
• fytogenní protinádorové látky MeSH
• inhibitor p15 cyklin-dependentní kinasy MeSH
• kurkumin MeSH
• nádorové proteiny MeSH
• reaktivní formy kyslíku MeSH