Author/Authors :
Ren، نويسنده , , Hui and Zhao، نويسنده , , Liqun and Li، نويسنده , , Yikun and Yue، نويسنده , , Ping and Deng، نويسنده , , Xingming and Owonikoko، نويسنده , , Taofeek K. and Chen، نويسنده , , Mingwei and Khuri، نويسنده , , Fadlo R. and Sun، نويسنده , , Shi-Yong، نويسنده ,
Abstract :
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.
Keywords :
PI3 Kinase , lung cancer , apoptosis , TRAIL , BKM120
