کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5506615 1400300 2016 24 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Selective killing of cancer cells by small molecules targeting heat shock stress response
ترجمه فارسی عنوان
کشتن انتخاب سلول های سرطانی با استفاده از مولکول های کوچک و هدف قرار دادن پاسخ استرس شوک گرما
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
چکیده انگلیسی
HSF1 heat shock response has emerged as a valuable non-oncogenetic intervention point in targeted cancer therapy. Current reporter based high throughput screening has led to the discovery of several compounds or chemotypes that are effective in the growth inhibition of multiple cancer cell lines and relevant animal tumor models. However, some intrinsic limitations of reporter based assays can potentially lead to biased results. Using a previously validated high content image based assay, we performed a phenotypic screen targeting HSF1 heat shock pathway with a chemically diversified library of over 100,000 compounds. Several novel functional inhibitors of HSF1 pathway were identified with different chemotypes. Western blot analysis confirmed that selective compounds inhibit phosphorylation of HSF1, followed by reduced expression of HSP proteins. Moreover, HeLa cells stably transfected with HSF1 shRNA were more resistant to the compound treatment under lethal temperature than cells containing HSF1, validating HSF1 dependent mechanism of action. These compounds demonstrate nanomolar potency toward multiple cancer cell lines with relatively low cytotoxicity to normal cells. Further SAR and target identification study will pave the way for the potential development of next generation anticancer drugs.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 478, Issue 4, 30 September 2016, Pages 1509-1514
نویسندگان
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