کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2513833 1118437 2009 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
AMP-activated protein kinase-dependent and -independent mechanisms underlying in vitro antiglioma action of compound C
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
AMP-activated protein kinase-dependent and -independent mechanisms underlying in vitro antiglioma action of compound C
چکیده انگلیسی

We investigated the effect of compound C, a well-known inhibitor of the intracellular energy sensor AMP-activated protein kinase (AMPK), on proliferation and viability of human U251 and rat C6 glioma cell lines. Compound C caused G2/M cell cycle block, accompanied by apoptotic glioma cell death characterized by caspase activation, phosphatidylserine exposure and DNA fragmentation. The mechanisms underlying the pro-apoptotic action of compound C involved induction of oxidative stress and downregulation of antiapoptotic molecule Bcl-2, while no alteration of pro-apoptotic Bax was observed. Compound C diminished AMPK phosphorylation and enzymatic activity, resulting in reduced phosphorylation of its target acetyl CoA carboxylase. AMPK activators metformin and AICAR partly prevented the cell cycle block, oxidative stress and apoptosis induced by compound C. The small interfering RNA (siRNA) targeting of human AMPK mimicked compound C-induced G2/M cell cycle arrest, but failed to induce oxidative stress and apoptosis in U251 glioma cells. In conclusion, our data indicate that AMPK inhibition is required, but not sufficient for compound C-mediated apoptotic death of glioma cells.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 77, Issue 11, 1 June 2009, Pages 1684–1693
نویسندگان
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