Comparison between Anthracyclines and Rhodamine-123 Accumulation in Chronic Lymphoid Leukemia: Effect of Cyclosporin A and Verapamil

Abstract

Multidrug resistance in leukemic cells is associated with decreased drug accumulation. A resistant cell line and cells from 11 patients with chronic lymphoid leukemia B were used for the evaluation of intracellular accumulation of daunorubicin (DNR), idarubicin (IDA), epirubicin (EPI) and rhodamine-123 (Rh-123). Cyclosporin A (CSA) and verapamil were used to test their modulatory effects on anthracyclines and the fluorescent dye. In leukemic samples there was a tendency for a lower accumulation index in samples tested with Rh-123 as compared to anthracyclines. IDA was a poorer substrate to P-glycoprotein (Pgp) than two of its analogues, e.g. DNR and EPI. A good correlation (80%) was found between Rh-123 accumulation and Pgp expression by phosphatase-anti-alkaline phosphatase. A strict correlation (100%) was found between modulation by CSA of Rh-123 accumulation and immunoreactivity to Pgp. Two discordant results were seen suggesting that other mechanisms of resistance could be present. The Rh-123 accumulation test seems to give a better indication than anthracyclines, however, it is not selective and may allow the detection of other drug-transport pumps.

Carrier-Mediated Uptake of Rhodamine 123: Implications on Its Use for MDR Research

“…When used as a molecular probe for study of P-gp activity, it is customary to either follow the accumulation (21)(22)(23)(24) or release (23,25,26) of R123 in the presence or absence of P-gp modulators. If the P-gp modulators were to increase R123 accumulation, a conclusion for the presence of P-gp activity is usually drawn.…”

Flow cytometry analysis of drug transport mechanisms in Haemonchus contortus susceptible or resistant to anthelmintics

“…Treatment with both R123 and a modulator of MDR appeared to provide more speci®c information on the possible role of Pgp (Canitrot et al 1996;Broxterman et al 1997;Maia et al 1998). Actually, VPL signi®cantly increased the retention of R123 by eggs, especially by HcR eggs.…”

Paired image‐ and FACS‐based toxicity assays for high content screening of spheroid‐type tumor cell cultures

“…To prevent the fluorescent dyes from being pumped out of the colonospheres by ATP binding cassette transporters [16,17] , Verapamil 50 μM was added to each well. Plates were placed in a humidified 37 °C incubator with 5% CO 2 for 30 min before adding the fluorescent dyes.…”