Article ID Journal Published Year Pages File Type
2112835 Cancer Letters 2013 10 Pages PDF
Abstract

•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.

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Life Sciences Biochemistry, Genetics and Molecular Biology Cancer Research
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