کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9891512 | 1540763 | 2005 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Resveratrol modulates gene expression associated with apoptosis, proliferation and cell cycle in cells with mutated human c-Ha-Ras, but does not alter c-Ha-Ras mRNA or protein expression
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کلمات کلیدی
terminal deoxynucleotidyl transferase biotin-dUTP nick end labelingp53GAPDHDMSO - DMSOROS - ROSsodium dodecyl sulfate-polyacrylamide gel electrophoresis - الکتروفورز ژل دوده سولفات سدیم پلی آکریل آمیدSDS-PAGE - الکتروفورز ژل پلی آکریل آمیدBrdU - بروموداکسی اوریدینbromodeoxyuridine - برومودسوویریدینProliferation - ترویجTUNEL - تونلApoptosis - خزان یاختهایDimethylsulfoxide - دیمتیل سولفواکسیدlactate dehydrogenase - لاکتات دهیدروژناز LDH - لاکتات دهیدروژناز به صورت مختصر شده LDH Ha-RAS - هکتار-RASPropidium iodide - پروتئین یدیدCell cycle - چرخه سلولیGlyceraldehyde phosphate dehydrogenase - گلیسرالیدید فسفات دهیدروژنازReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
An accumulating body of evidence suggests that resveratrol can inhibit carcinogenesis through antiproliferative and apoptotic effects. One proposed mechanism for this is the modulation of genes, for example, Ras and p53, frequently associated with human cancer. To test the effect of resveratrol on gene expression, we used the WR-21 cell line because it contains a mutated human c-Ha-ras gene. Cells at â¥70% confluency were incubated with media alone or with increasing concentrations of trans-resveratrol (0.1-1000 μM) for 24 h. Resveratrol (30-100 μM) decreased cellular proliferation by 80% (bromodeoxyuridine incorporation) and increased apoptosis by 60% (TUNEL). Cells were then treated with media alone or with 50-μM resveratrol for 24 h. RNA was isolated for nylon-based macroarray analyses and protein for immunoblotting. Resveratrol increased (+) and decreased (â) gene expression associated with apoptosis (Birc5+, Cash+, Mcl-1+, Mdm2+, Rpa-like+), cellular proliferation (Ctsd+, Mdm2+, Egr1+, ODC+) and cell cycle (cyclin D+, cyclin g+, Gadd45aâ, Mad2lâ, Mdm2+). Resveratrol consistently increased by â¥6-fold Mdm2 expression and other downstream p53 effectors, but not p53 itself at 24 h. Subsequent cell cycle analysis indicated a significant accumulation of cells in G2/M, and a decrease in G1/G0 suggesting a G2/M blockade. Further RT-PCR and Western blot analyses indicated no differential changes in Ras mRNA expression or p21ras protein levels, respectively. These results suggest that resveratrol potently inhibits cellular proliferation, increases apoptosis, alters cell cycle dynamics and modulates associated gene expression. Furthermore, these effects appear mediated, in part, by p53 without direct modulation of mutant c-Ha-ras expression.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Journal of Nutritional Biochemistry - Volume 16, Issue 11, November 2005, Pages 663-674
Journal: The Journal of Nutritional Biochemistry - Volume 16, Issue 11, November 2005, Pages 663-674
نویسندگان
Leeanne F. Young, Holly L. Hantz, Keith R. Martin,