BACKGROUND: We have recently shown that high-level expression of the multidrug resistance-associated protein (MRP) gene is a powerful independent predictor of poor outcome in neuroblastoma. The clinical implication of these findings is that MRP modulators may prove therapeutically useful. PROCEDURE: We therefore investigated the ability of difloxacin, a quinolone antimicrobial antibiotic, to increase drug cytotoxicity in unselected cultured human neuroblastoma cells. Drug cytotoxicity was determined using a microtiter assay in neuroblastoma cells expressing low (SH-EP), intermediate (NBL-S), or high [BE(2)-C] levels of MRP. RESULTS: Difloxacin (50 microg/ml) increased sensitivity to the MRP substrates, vincristine, doxorubicin, daunorubicin, and potassium antimony tartrate to an extent directly proportional to their level of MRP expression. No change in the response to cisplatin, which is not a substrate for MRP, was observed in any of the cell lines. CONCLUSIONS: The data demonstrate that difloxacin can reverse drug resistance in unselected human neuroblastoma cells and is therefore a potential candidate for future clinical trials.
BACKGROUND: We have recently shown that high-level expression of the multidrug resistance-associated protein (MRP) gene is a powerful independent predictor of poor outcome in neuroblastoma. The clinical implication of these findings is that MRP modulators may prove therapeutically useful. PROCEDURE: We therefore investigated the ability of difloxacin, a quinolone antimicrobial antibiotic, to increase drug cytotoxicity in unselected cultured humanneuroblastoma cells. Drug cytotoxicity was determined using a microtiter assay in neuroblastoma cells expressing low (SH-EP), intermediate (NBL-S), or high [BE(2)-C] levels of MRP. RESULTS:Difloxacin (50 microg/ml) increased sensitivity to the MRP substrates, vincristine, doxorubicin, daunorubicin, and potassium antimony tartrate to an extent directly proportional to their level of MRP expression. No change in the response to cisplatin, which is not a substrate for MRP, was observed in any of the cell lines. CONCLUSIONS: The data demonstrate that difloxacin can reverse drug resistance in unselected humanneuroblastoma cells and is therefore a potential candidate for future clinical trials.
Authors: Leonidas A Bourikas; George Kolios; Vassilis Valatas; George Notas; Ioannis Drygiannakis; Iordanis Pelagiadis; Pinelopi Manousou; Stefanos Klironomos; Ioannis A Mouzas; Elias Kouroumalis Journal: Br J Pharmacol Date: 2009-04-09 Impact factor: 8.739
Authors: Catherine A Burkhart; Fujiko Watt; Jayne Murray; Marina Pajic; Anatoly Prokvolit; Chengyuan Xue; Claudia Flemming; Janice Smith; Andrei Purmal; Nadezhda Isachenko; Pavel G Komarov; Katerina V Gurova; Alan C Sartorelli; Glenn M Marshall; Murray D Norris; Andrei V Gudkov; Michelle Haber Journal: Cancer Res Date: 2009-08-04 Impact factor: 12.701
Authors: Kyoung won Seo; Roseline Holt; Yong-Sam Jung; Carlos O Rodriguez; Xinbin Chen; Robert B Rebhun Journal: PLoS One Date: 2012-08-21 Impact factor: 3.240