کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2107843 1083705 2010 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Itraconazole, a Commonly Used Antifungal that Inhibits Hedgehog Pathway Activity and Cancer Growth
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Itraconazole, a Commonly Used Antifungal that Inhibits Hedgehog Pathway Activity and Cancer Growth
چکیده انگلیسی

SummaryIn a screen of drugs previously tested in humans we identified itraconazole, a systemic antifungal, as a potent antagonist of the Hedgehog (Hh) signaling pathway that acts by a mechanism distinct from its inhibitory effect on fungal sterol biosynthesis. Systemically administered itraconazole, like other Hh pathway antagonists, can suppress Hh pathway activity and the growth of medulloblastoma in a mouse allograft model and does so at serum levels comparable to those in patients undergoing antifungal therapy. Mechanistically, itraconazole appears to act on the essential Hh pathway component Smoothened (SMO) by a mechanism distinct from that of cyclopamine and other known SMO antagonists, and prevents the ciliary accumulation of SMO normally caused by Hh stimulation.

Graphical AbstractFigure optionsDownload high-quality image (369 K)Download as PowerPoint slideHighlights
► Itraconazole identified as Hh pathway inhibitor in screen of human-experienced drugs
► Itraconazole appears to act on Smoothened at distinct site from cyclopamine
► Itraconazole inhibits accumulation of Smoothened in primary cilium
► Itraconazole suppresses Hh-dependent tumor growth in vivo

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 17, Issue 4, 13 April 2010, Pages 388–399
نویسندگان
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