ABCMdb

PMID: 16753135

Park SJ, Wu CH, Choi MR, Najafi F, Emami A, Safa AR
P-glycoprotein enhances TRAIL-triggered apoptosis in multidrug resistant cancer cells by interacting with the death receptor DR5.
Biochem Pharmacol. 2006 Jul 28;72(3):293-307. Epub 2006 May 4., [PubMed]

Sentences

No. Mutations Sentence Comment

138 ABCB1 p.Gly185Val It is therefore intriguing that TRAIL induced much more apoptosis in the KB-3-1 transfectant KB-VSV1, which expresses the mutant G185V P-gp, than in the wt P-gp transfectant KB-GSV2 (Table 1) (see Section 4). Login to comment 139 ABCB1 p.Gly185Val It is therefore intriguing that TRAIL induced much more apoptosis in the KB-3-1 transfectant KB-VSV1, which expresses the mutant G185V P-gp, than in the wt P-gp transfectant KB-GSV2 (Table 1) (see Section 4). Login to comment 296 ABCB1 p.Gly185Val ABCB1 p.Gly185Val The immunoblot was probed for the presence of (A) DR5, (B) DR4, (C) DcR1, and P-gp as described in Section 2. in cells transfected with the MDR1 and overexpressing P-gp; (2) treating P-gp-expressing BC-19 cells with the anti-P-gp monoclonal antibody MRK-16 decreased TRAIL-induced apoptosis to similar levels induced in their drug-sensitive counterparts; (3) TRAIL induced preferential apoptosis in P-gp-overexpressing cells by depleting ATP and increasing the ATPase activity of P-gp; (4) KB-VSV1 transfectants with P-gp mutated at position 185 (glycine-185 to valine, G185V) underwent much more TRAIL-induced apoptosis than the transfectants expressing wild-type P-gp. Login to comment 297 ABCB1 p.Gly185Val ABCB1 p.Gly185Val ABCB1 p.Gly185Val ABCB1 p.Gly185Val The immunoblot was probed for the presence of (A) DR5, (B) DR4, (C) DcR1, and P-gp as described in Section 2. in cells transfected with the MDR1 and overexpressing P-gp; (2) treating P-gp-expressing BC-19 cells with the anti-P-gp monoclonal antibody MRK-16 decreased TRAIL-induced apoptosis to similar levels induced in their drug-sensitive counterparts; (3) TRAIL induced preferential apoptosis in P-gp- overexpressing cells by depleting ATP and increasing the ATPase activity of P-gp; (4) KB-VSV1 transfectants with P-gp mutated at position 185 (glycine-185 to valine, G185V) underwent much more TRAIL-induced apoptosis than the transfectants expressing wild-type P-gp. Login to comment 298 ABCB1 p.Gly185Val ABCB1 p.Gly185Val The superior TRAIL sensitization elicited by G185V P-gp strengthens the linkage between P-gp transporter function and enhancement of TRAIL-induced apoptosis, because thermodynamic analysis has revealed that G185V P-gp is more efficient in the ATP-dependent transport of substrates than wt P-gp, owing to a lower Arrhenius activation energy for the rate-limiting step of ATP hydrolysis-coupled substrate transport [31]. Login to comment