کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5824267 | 1118471 | 2008 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Alpha anomer of 5-aza-2â²-deoxycytidine down-regulates hTERT mRNA expression in human leukemia HL-60 cells
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کلمات کلیدی
PLAGAPDHSAMACTCCCTC binding factorS-adenosyl-l-homocysteineG6PDH5-AzacytidineCTCFSAHPBGDTBPRNA polymerase II - آرانای پلیمراز II 5-Aza-2′-deoxycytidine - 5-Aza-2'-deoxycytidinec-Myc - c-mychTERT - htertS-adenosyl-L-methionine - S-adenosyl-L-metionineTATA box-binding protein - TATA جعبه اتصال پروتئینβ-actin - β-اکتینphospholipase A2 - آنزیم فسفولیپاز A2 human telomerase reverse transcriptase - تلومراز انسانی معکوس transcriptaseDNA hypomethylation - دی ان ای متیلسیون DNAHistone acetyltransferase - هیستون استیل ترانسفرازporphobilinogen deaminase - پورفبیلینوژن دامینازHAT - کلاهglucose-6-phosphate dehydrogenase - گلوکز 6-فسفات دهیدروژنازglyceraldehyde-3-phosphate-dehydrogenase - گلیسرولیدید 3-فسفات دهیدروژناز
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Alpha anomer of 5-aza-2â²-deoxycytidine down-regulates hTERT mRNA expression in human leukemia HL-60 cells Alpha anomer of 5-aza-2â²-deoxycytidine down-regulates hTERT mRNA expression in human leukemia HL-60 cells](/preview/png/5824267.png)
چکیده انگلیسی
DNA methylation inhibitors are being extensively studied as potential anticancer agents. In the present study, we compared the capability of alpha anomer of 5-aza-2â²-deoxycytidine (α-5-azadCyd) to induce down-regulation of hTERT expression in HL-60 cells with other nucleoside analogs that act as DNA methylation inhibitors: β-5-azadCyd (decitabine), (S)-9-(2,3-dihydroxypropyl)adenine [(S)-DHPA], isobutyl ester of (R,S)-3-(adenin-9-yl)-2-hydroxypropanoic acid [(R,S)-AHPA-ibu] and prospective DNA methylation inhibitors (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine [(S)-HPMPazaC] and 5-fluoro-zebularine (F-PymRf). Exposure to α-5-azadCyd induced the down-regulation of hTERT expression in low micromolar concentrations (0.05-50 μM). A more cytotoxic beta anomer caused a transient up-regulation of hTERT and a subsequent reduction in hTERT mRNA levels at concentrations more than 10 times below its GIC50 value. In this respect, (S)-DHPA and (R,S)-AHPA-ibu were less efficient, since a similar effect was achieved at concentrations above their GIC50. In contrast, F-PymRf treatment resulted in up to a three-fold induction of hTERT expression within a broad range of concentrations. In all cases, the down-regulation of hTERT expression was concentration-dependent. The correlation was found between c-myc overexpression and transiently elevated hTERT expression after treatment with all tested compounds except for α-5-azadCyd and (S)-HPMPazaC. Although the primary task of hypomethylating agents in anticancer therapy lies in reactivation of silenced tumour-suppressor genes, the inhibition of hTERT expression might also be a fruitful clinical effect of this approach.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 75, Issue 4, 15 February 2008, Pages 965-972
Journal: Biochemical Pharmacology - Volume 75, Issue 4, 15 February 2008, Pages 965-972
نویسندگان
Miroslav Hájek, Ivan Votruba, AntonÃn Holý, Marcela KreÄmerová, Eva TlouÅ¡t'ová,