کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10901020 | 1084678 | 2016 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibitions of mTORC1 and 4EBP-1 are key events orchestrated by Rottlerin in SK-Mel-28 cell killing
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کلمات کلیدی
LKB1Sulforhodaminep90RSKsequestosome 1necrostatin-1LC3-IIBeclin-1PARP3-MAp70S6KPMSFRPMImTORTCASRBACCAMPK3-methyladenine - 3-متیل آدنینAMP-activated protein kinase - AMP-پروتئین کیناز فعال شده استNec-1 - NEC-1p70 ribosomal protein S6 kinase - P70 پروتئین ریبوزومی S6 کینازp90 ribosomal S6 kinase - S6 kinase ribosomal p90Autophagy - اتوفاژیacetyl-CoA carboxylase - استیل کروکسی سیلازtrichloroacetic acid - اسید ترشکلراکتیکRottlerin - رتلرینRaptor - رپتورProtein synthesis - سنتز پروتئینphenylmethylsulfonyl fluoride - فنیل متیل سولفونیل فلورایدlactate dehydrogenase - لاکتات دهیدروژناز LDH - لاکتات دهیدروژناز به صورت مختصر شده LDH mammalian target of rapamycin - هدف پستانداران رپامایسینregulatory-associated protein of mTOR - پروتئین مرتبط با تنظیم کننده mTORPoly(ADP-ribose) polymerase - پلیمر (ADP-ribose) پلیمرازChloroquine - کلروکین liver kinase B1 - کیناز کیناز B1
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Earlier studies demonstrated that Rottlerin exerts a time- and dose-dependent antiproliferative effect on SK-Mel-28 melanoma cells during 24âh of treatment, but cytotoxicity due to cell death began only after a 48âh exposure. In the current study, in order to identify the type of cell death in this cell line, which is notoriously refractory to most anticancer therapies, and to clarify the underlying mechanisms of this delayed outcome, we searched for apoptotic, necrotic/necroptotic and autophagic traits in Rottlerin-exposed cells. Although SK-Mel-28 cells are both apoptosis and autophagy competent, Western blotting analysis, caspase activity assay, nuclear imaging and the effects of autophagy, apoptosis and necroptosis inhibitors, indicated that Rottlerin cytotoxicity was due to none of the aforementioned death mechanisms. Nevertheless, in growth arrested cells, the death did occur after a prolonged treatment and most likely ensued from the observed blockage of protein synthesis that reached levels expected to be incompatible with cell survival. From a mechanistic point of view, we ascribed this effect to the documented inhibition of mTORC1 activity; mTORC1 inhibition on the one hand led to a not deadly, rather protective autophagic response but, on the other hand caused a near complete arrest of protein synthesis. Interestingly, no cytotoxicity was found towards normal skin fibroblasts, which only resulted mildly growth arrested by the drug.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 380, Issue 1, 28 September 2016, Pages 106-113
Journal: Cancer Letters - Volume 380, Issue 1, 28 September 2016, Pages 106-113
نویسندگان
E. Daveri, E. Maellaro, G. Valacchi, F. Ietta, M. Muscettola, E. Maioli,