کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2112835 1084426 2013 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The PI3 kinase inhibitor NVP-BKM120 induces GSK3/FBXW7-dependent Mcl-1 degradation, contributing to induction of apoptosis and enhancement of TRAIL-induced apoptosis
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
The PI3 kinase inhibitor NVP-BKM120 induces GSK3/FBXW7-dependent Mcl-1 degradation, contributing to induction of apoptosis and enhancement of TRAIL-induced apoptosis
چکیده انگلیسی


• The novel PI3K inhibitor, BKM120, induces apoptosis and enhance TRAIL-induced apoptosis.
• BKM120 induces GSK3-dependent and FBXW7-mediated Mcl-1 degradation.
• Mcl-1 reduction contributes to induction of apoptosis and enhancement of TRAIL-induced apoptosis by BKM120.

This study focuses on determining whether and how the novel PI3 kinase inhibitor NVP-BKM120 (BKM120) induces apoptosis and enhances TRAIL-induced apoptosis in human lung cancer cells. We found that BKM120 reduced Mcl-1 levels across the tested cell lines along with induction of apoptosis and enhancement of TRAIL-induced apoptosis. Enforced expression of ectopic Mcl-1 significantly attenuated the effects of BKM120 alone or in combination with TRAIL on induction of apoptosis. Thus Mcl-1 downregulation contributes to BKM120-induced apoptosis or enhancement of TRAIL-induced apoptosis. Moreover, we have demonstrated that BMK120 decreases Mcl-1 levels through facilitating its degradation involving a GSK3/FBXW7-dependent mechanism.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 338, Issue 2, 28 September 2013, Pages 229–238
نویسندگان
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