Publication Date:
2015-11-26
Description:
Publication date: Available online 25 November 2015 Source: FEBS Letters Author(s): Ryuji Yamaguchi, Guy Perkins, Kiichi Hirota We found that targeting cholesterol with beta-cyclodextrin (bCD) and its derivatives disrupted signal transduction between PI3K and AKT, attenuating AKT pro-survival signals. In their absence, 2-deoxyglucose (2DG) caused anti-apoptotic protein Mcll to dissociate from pro-apoptotic Bak at mitochondria. Normally Bak is sequestered by its inhibitory associations with Mcll and Bcl-xL, and only when Bak is released from both, is it free to form oligomers through which cytochrome c can escape into the cytosol. Thus an addition of a bcl-2 antagonist dissociates Bak from Bcl-xL, triggering cytochrome c release and inducing apoptosis. 2DG–bCD can also sensitize type II cancer cells for TRAIL-mediated apoptosis.
Print ISSN:
0014-5793
Electronic ISSN:
1873-3468
Topics:
Biology
,
Chemistry and Pharmacology
,
Physics
