کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10899485 | 1084380 | 2015 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A novel apoptosis-inducing mechanism of 5-aza-2â²-deoxycitidine in melanoma cells: Demethylation of TNF-α and activation of FOXO1
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کلمات کلیدی
mAbMSPFOXO15-Aza - 5-نهMethylation-specific PCR - PCR اختصاصی متیلاتMonoclonal antibody - آنتی بادی مونوکلونالchromatin immunoprecipitation - ایمن سازی کروماتینbisulfite sequencing - توالی بیسولفیتtumor necrosis factor-α - تومور نکروز عامل αforkhead Box O - جعبه O جعبه OMelanoma - خال سرطانی یا ملانوماApoptosis - خزان یاختهایFas Ligand - فاس لیگاندFasL - فاسدTNF-α - فاکتور نکروز توموری آلفاFoxO - فاکسوTRAIL - قطارTNF-related apoptosis-inducing ligand - لیگاند ناشی از آپوپتوز مرتبط با TNFCHiP - چیپ
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Melanoma is a poor-prognosis cancer in both humans and dogs, and so the anti-tumor effects of 5-aza-2â²-deoxycitidine (5-aza) on solid tumors such as melanoma have gained much attention. However, its anti-tumor mechanism remains entirely unclear. This present study revealed a part of the anti-tumor effects of 5-aza, focusing on apoptosis induction, on human and canine melanoma cells. Treatment with 5-aza markedly induced obvious apoptosis in melanoma cells. 5-Aza-induced apoptosis was possibly due to induced expression of cytotoxic cytokines such as TNF-α. We revealed hypermethylation of the promoter region of TNF-α as a consequence of treatment with 5-aza. Concurrently, we evaluated the effect of 5-aza on the Akt/FOXO1 signaling cascade, which plays a pivotal role in the transcription of cytokine genes. As a result, 5-aza inactivated Akt and inversely activated FOXO1, which contributed to the up-regulation of TNF-α. Furthermore, up-regulation of TNF-α by 5-aza administration was found in in vivo experiments. These current data suggest a novel apoptosis-inducing mechanism of 5-aza and indicate that 5-aza could be a promising therapeutic agent for the treatment of human and canine melanomas.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 369, Issue 2, 28 December 2015, Pages 344-353
Journal: Cancer Letters - Volume 369, Issue 2, 28 December 2015, Pages 344-353
نویسندگان
Shunsuke Noguchi, Takashi Mori, Masaya Igase, Takuya Mizuno,