Idarubicin DNA intercalation is reduced by MRP1 and not Pgp

Mutational analysis of P-glycoprotein: suppression of caspase activation in the absence of ATP-dependent drug efflux

“…18 Our data demonstrated for the first time that an ATPasedefective form of P-gp incapable of effluxing substrate drugs still regulated drug-induced cell death. These findings were strengthened by our demonstration that apoptosis induced by idarubicin, a poor substrate for P-gp, 36 was equivalently inhibited in CEM-P-gp WT and CEM-P-gp MM cells. Moreover, P-gp WT and P-gp MM equivalently suppressed apoptosis mediated by growth factor withdrawal, consistent with previous demonstrations that wild-type P-gp provided a survival advantage to cells grown in reduced serum.…”

“…These data are representative of at least three separate experiments Drug resistance by ATPase-defective P-gp KM Tainton et al sensitivity of CEM-GFP, CEM-P-gp WT and CEM-P-gp MM cells to apoptosis induced by idarubicin, which is a poor substrate for wild-type P-gp. 36 As shown in Figure 6a, CEM-GFP cells were highly sensitive to idarubicin-induced apoptosis, while CEM-P-gp WT , CEM-P-gp MM-3 and CEM-P-gp MM-32 cells were significantly less sensitive. Importantly, there was no difference in the relative sensitivity of cells expressing wild type or ATPase mutant P-gp to idarubicin.…”

Down-regulation of Intrinsic P-glycoprotein Expression in Multicellular Prostate Tumor Spheroids by Reactive Oxygen Species

“…A comparable chemosensitization in EMT-6 tumor spheroids was observed by treatment with hyaluronidase, which reduced intercellular communication and activated cell proliferation (40). Furthermore, stimulation of cell proliferation in noncycling hematopoietic progenitor cells and leukemic blasts resulted in a down-regulation of Pgp-mediated MDR (41). An elevation of ROS by depletion of intracellular glutathione sounds reasonable, because BSO has successfully been applied in vivo in cancer patients and was shown to increase the sensitivity of cancer cells toward antineoplastic drugs (42).…”

Drug Efflux Transporters and Multidrug Resistance in Acute Leukemia: Therapeutic Impact and Novel Approaches to Mediation

“…For example, studies with MRP ϩ NB4 and HL-60 cells showed that gemtuzumab ozogamicin-induced cytotoxicity was attenuated with MRP1 expression (Walter et al, 2003). Furthermore, MRP1 expression was shown to reduce DNA intercalation of daunorubicin and idarubicin (Smeets et al, 1999) and to be up-regulated in AML-2/DX300 (Kweon et al, 2010) and HL60/DOX (Baran et al, 2007) doxorubicin-resistant AML cells. MRP1 was found to be overexpressed in an arsenic trioxide-resistant human leukemia cell line, K562/AS-3 (Seo et al, 2007).…”