The PI3 kinase inhibitor NVP-BKM120 induces GSK3/FBXW7-dependent Mcl-1 degradation, contributing to induction of apoptosis and enhancement of TRAIL-induced apoptosis

详细信息    查看全文

• 作者：Hui Ren ; Liqun Zhao ; Yikun Li ; Ping Yue ; Xingming Deng ; Taofeek K. Owonikoko ; Mingwei Chen ; Fadlo R. Khuri ; Shi-Yong Sun
• 关键词：BKM120 ; PI3 kinase ; TRAIL ; Apoptosis ; Lung cancer
• 刊名：Cancer Letters
• 出版年：2013
• 出版时间：28 September, 2013
• 年：2013
• 卷：338
• 期：2
• 页码：229-238
• 全文大小：1463 K

文摘

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.