Glucosylceramide synthase inhibitors sensitise CLL cells to cytotoxic agents without reversing P-gp functional activity

European Journal of Pharmacology

Volumn 609, Issue 1-3, 2009, Pages 34-39

  Gerrard, Gareth ^a   Butters, Terry D ^b   Ganeshaguru, Kanagasabai ^a   Mehta, Atul B ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

CLL; Gaucher Disease; Glucosylceramide synthase inhibitor; MDR; P glycoprotein

Indexed keywords

CERAMIDE GLUCOSYLTRANSFERASE INHIBITOR; CHLORAMBUCIL; CLADRIBINE; CYTOTOXIC AGENT; FLUDARABINE; GLUCOSYLCERAMIDE; GLYCOPROTEIN P; N BUTYL DEOXYGALACTONOJIRIMYCIN; N NONYL DEOXYGALACTONOJIRIMYCIN; UNCLASSIFIED DRUG; VINCRISTINE;

ADULT; AGED; ARTICLE; CHRONIC LYMPHATIC LEUKEMIA; CLINICAL ARTICLE; CONTROLLED STUDY; CYTOTOXICITY; DRUG ACTIVITY; DRUG POTENTIATION; DRUG SENSITIZATION; FEMALE; HUMAN; HUMAN CELL; IC 50; MALE; PRIORITY JOURNAL; PROTEIN EXPRESSION;

1-DEOXYNOJIRIMYCIN; AGED; AGED, 80 AND OVER; B-LYMPHOCYTES; CELL LINE, TUMOR; CHLORAMBUCIL; CYTOTOXINS; ENZYME INHIBITORS; FEMALE; FLUORESCEINS; FLUORESCENT DYES; FORMAZANS; GLUCOSYLTRANSFERASES; HUMANS; INHIBITORY CONCENTRATION 50; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MALE; MIDDLE AGED; MODELS, CHEMICAL; MOLECULAR STRUCTURE; P-GLYCOPROTEIN; TETRAZOLIUM SALTS; VIDARABINE;

EID: 64549125120     PISSN: 00142999     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ejphar.2009.03.018     Document Type: Article

References (47)

1. Advani R., Saba H.I., Tallman M.S., Rowe J.M., Wiernik P.H., Ramek J., Dugan K., Lum B., Villena J., Davis E., Paietta E., Litchman M., Sikic B.I., and Greenberg P.L. Treatment of refractory and relapsed acute myelogenous leukemia with combination chemotherapy plus the multidrug resistance modulator PSC 833 (Valspodar). Blood 93 (1999) 787-795
2. Andersson U., Butters T.D., Dwek R.A., and Platt F.M. N-butyldeoxygalactonojirimycin: a more selective inhibitor of glycosphingolipid biosynthesis than N-butyldeoxynojirimycin, in vitro and in vivo. Biochem. Pharmacol. 59 (2000) 821-829
3. Beck W.T., and Cirtain M.C. Continued expression of vinca alkaloid resistance by CCRF-CEM cells after treatment with tunicamycin or pronase. Cancer Res. 42 (1982) 184-189
4. Bieberich E., Freischutz B., Suzuki M., and Yu R.K. Differential effects of glycolipid biosynthesis inhibitors on ceramide-induced cell death in neuroblastoma cells. J. Neurochem. 72 (1999) 1040-1049
5. Bohm P., Kunz W., Horny H.P., and Einsele H. Adult Gaucher disease in association with primary malignant bone tumors. Cancer 91 (2001) 457-462
6. Butters T.D., Dwek R.A., and Platt F.M. New therapeutics for the treatment of glycosphingolipid lysosomal storage diseases. Adv. Exp. Med. Biol. 535 (2003) 219-226
7. Consoli U., Santonocito A., Stagno F., Fiumara P., Privitera A., Parisi G., Giustolisi G.M., Pavone B., Palumbo G.A., Di Raimondo F., Milone G., Guglielmo P., and Giustolisi R. Multidrug resistance mechanisms in chronic lymphocytic leukaemia. Br. J. Haematol. 116 (2002) 774-780
8. Cox T., Lachmann R., Hollak C., Aerts J., Van Weely S., Hrebicek M., Platt F., Butters T., Dwek R., Moyses C., Gow I., Elstein D., and Zimran A. Novel oral treatment of Gaucher's disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis. Lancet 355 (2000) 1481-1485
9. Dantzig A.H., Shepard R.L., Cao J., Law K.L., Ehlhardt W.J., Baughman T.M., Bumol T.F., and Starling J.J. Reversal of P-glycoprotein-mediated multidrug resistance by a potent cyclopropyldibenzosuberane modulator, LY335979. Cancer Res. 56 (1996) 4171-4179
10. Elstein D., Hollak C., Aerts J.M., Van Weely S., Maas M., Cox T.M., Lachmann R.H., Hrebicek M., Platt F.M., Butters T.D., Dwek R.A., and Zimran A. Sustained therapeutic effects of oral miglustat (Zavesca, N-butyldeoxynojirimycin, OGT 918) in type I Gaucher disease. J. Inherit. Metab. Dis. 27 (2004) 757-766
11. Ganeshaguru K., Wickremasinghe R.G., Jones D.T., Gordon M., Hart S.M., Virchis A.E., Prentice H.G., Hoffbrand A.V., Man A., Champain K., Csermak K., and Mehta A.B. Actions of the selective protein kinase C inhibitor PKC412 on B-chronic lymphocytic leukemia cells in vitro. Haematologica 87 (2002) 167-176
12. Gerrard G., Payne E., Baker R.J., Jones D.T., Potter M., Prentice H.G., Ethell M., McCullough H., Burgess M., Mehta A.B., and Ganeshaguru K. Clinical effects and P-glycoprotein inhibition in patients with acute myeloid leukemia treated with zosuquidar trihydrochloride, daunorubicin and cytarabine. Haematologica 89 (2004) 782-790
13. Gottesman M.M., Fojo T., and Bates S.E. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat. Rev. Cancer 2 (2002) 48-58
14. Gouaze-Andersson V., and Cabot M.C. Glycosphingolipids and drug resistance. Biochim. Biophys. Acta 1758 (2006) 2096-2103
15. Green L.J., Marder P., and Slapak C.A. Modulation by LY335979 of P-glycoprotein function in multidrug-resistant cell lines and human natural killer cells. Biochem. Pharmacol. 61 (2001) 1393-1399
16. Hunault M., Zhou D., Delmer A., Ramond S., Viguie F., Cadiou M., Perrot J.Y., Levy V., Rio B., Cymbalista F., Zittoun R., and Marie J.P. Multidrug resistance gene expression in acute myeloid leukemia: major prognosis significance for in vivo drug resistance to induction treatment. Ann. Hematol. 74 (1997) 65-71
17. Itoh M., Kitano T., Watanabe M., Kondo T., Yabu T., Taguchi Y., Iwai K., Tashima M., Uchiyama T., and Okazaki T. Possible role of ceramide as an indicator of chemoresistance: decrease of the ceramide content via activation of glucosylceramide synthase and sphingomyelin synthase in chemoresistant leukemia. Clin. Cancer Res. 9 (2003) 415-423
18. Jamroziak K., Smolewski P., Cebula B., Szmigielska-Kaplon A., Darzynkiewicz Z., and Robak T. Relation of P-glycoprotein expression with spontaneous in vitro apoptosis in B-cell chronic lymphocytic leukemia. Neoplasma 51 (2004) 181-187
19. Juliano R.L., and Ling V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim. Biophys. Acta 455 (1976) 152-162
20. Karaszi E., Jakab K., Homolya L., Szakacs G., Hollo Z., Telek B., Kiss A., Rejto L., Nahajevszky S., Sarkadi B., and Kappelmayer J. Calcein assay for multidrug resistance reliably predicts therapy response and survival rate in acute myeloid leukaemia. Br. J. Haematol. 112 (2001) 308-314
21. Kok J.W., Veldman R.J., Klappe K., Koning H., Filipeanu C.M., and Muller M. Differential expression of sphingolipids in MRP1 overexpressing HT29 cells. Int. J. Cancer 87 (2000) 172-178
22. Krishnan B., Ganeshaguru K., Baker R., Richfield L., and Mehta A.B. Multidrug resistance and myelomonocytic leukaemia in Gaucher's disease. Haematologica 88 (2003) ECR02
23. Lavie Y., Cao H., Bursten S.L., Giuliano A.E., and Cabot M.C. Accumulation of glucosylceramides in multidrug-resistant cancer cells. J. Biol. Chem. 271 (1996) 19530-19536
24. Lavie Y., Cao H., Volner A., Lucci A., Han T.Y., Geffen V., Giuliano A.E., and Cabot M.C. Agents that reverse multidrug resistance, tamoxifen, verapamil, and cyclosporin A, block glycosphingolipid metabolism by inhibiting ceramide glycosylation in human cancer cells. J. Biol. Chem. 272 (1997) 1682-1687
25. Leith C.P., Kopecky K.J., Chen I.M., Eijdems L., Slovak M.L., McConnell T.S., Head D.R., Weick J., Grever M.R., Appelbaum F.R., and Willman C.L. Frequency and clinical significance of the expression of the multidrug resistance proteins MDR1/P-glycoprotein, MRP1, and LRP in acute myeloid leukemia: a Southwest Oncology Group Study. Blood 94 (1999) 1086-1099
26. Leonard G.D., Fojo T., and Bates S.E. The Role of ABC Transporters in Clinical Practice. Oncologist 8 (2003) 411-424
27. Liour S.S., and Yu R.K. Differential effects of three inhibitors of glycosphingolipid biosynthesis on neuronal differentiation of embryonal carcinoma stem cells. Neurochem. Res. 27 (2002) 1507-1512
28. List A.F., Kopecky K.J., Willman C.L., Head D.R., Persons D.L., Slovak M.L., Dorr R., Karanes C., Hynes H.E., Doroshow J.H., Shurafa M., and Appelbaum F.R. Benefit of cyclosporine modulation of drug resistance in patients with poor-risk acute myeloid leukemia: a Southwest Oncology Group study. Blood 98 (2001) 3212-3220
29. Liu Y.Y., Han T.Y., Giuliano A.E., and Cabot M.C. Expression of glucosylceramide synthase, converting ceramide to glucosylceramide, confers adriamycin resistance in human breast cancer cells. J. Biol. Chem. 274 (1999) 1140-1146
30. Lucci A., Cho W.I., Han T.Y., Giuliano A.E., Morton D.L., and Cabot M.C. Glucosylceramide: a marker for multiple-drug resistant cancers. Anticancer Res. 18 (1998) 475-480
31. Matutes E., Owusu-Ankomah K., Morilla R., Garcia M.J., Houlihan A., Que T.H., and Catovsky D. The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL. Leukemia 8 (1994) 1640-1645
32. Mellor H.R., Nolan J., Pickering L., Wormald M.R., Platt F.M., Dwek R.A., Fleet G.W., and Butters T.D. Preparation, biochemical characterization and biological properties of radiolabelled N-alkylated deoxynojirimycins. Biochem. J. 366 (2002) 225-233
33. Norris-Cervetto E., Callaghan R., Platt F.M., Dwek R.A., and Butters T.D. Inhibition of glucosylceramide synthase does not reverse drug resistance in cancer cells. J. Biol. Chem. 279 (2004) 40412-40418
34. Norris-Cervetto E., Butters T.D., Martin C., Modok S., Dwek R.A., and Callaghan R. Can P-glycoprotein influence the bioavailability of iminosugar-based glucosylceramide synthase inhibitors?. Eur. J. Pharmacol. 530 (2006) 195-204
35. Olshefski R.S., and Ladisch S. Glucosylceramide synthase inhibition enhances vincristine-induced cytotoxicity. Int. J. Cancer 93 (2001) 131-138
36. Oscier D., Fegan C., Hillmen P., Illidge T., Johnson S., Maguire P., Matutes E., and Milligan D. Guidelines on the diagnosis and management of chronic lymphocytic leukaemia. Br. J. Haematol. 125 (2004) 294-317
37. Platt F.M., Neises G.R., Dwek R.A., and Butters T.D. N-butyldeoxynojirimycin is a novel inhibitor of glycolipid biosynthesis. J. Biol. Chem. 269 (1994) 8362-8365
38. Platt F.M., Neises G.R., Karlsson G.B., Dwek R.A., and Butters T.D. N-butyldeoxygalactonojirimycin inhibits glycolipid biosynthesis but does not affect N-linked oligosaccharide processing. J. Biol. Chem. 269 (1994) 27108-27114
39. Radin N.S. Chemotherapy by slowing glucosphingolipid synthesis. Biochem. Pharmacol. 57 (1999) 589-595
40. Tepper A.D., Diks S.H., van Blitterswijk W.J., and Borst J. Glucosylceramide synthase does not attenuate the ceramide pool accumulating during apoptosis induced by CD95 or anti-cancer regimens. J. Biol. Chem. 275 (2000) 34810-34817
41. Turzanski J., Grundy M., Shang S., Russell N., and Pallis M. P-glycoprotein is implicated in the inhibition of ceramide-induced apoptosis in TF-1 acute myeloid leukemia cells by modulation of the glucosylceramide synthase pathway. Exp. Hematol. 33 (2005) 62-72
42. van Giersbergen P.L.M., and Dingemanse J. Influence of food intake on the pharmacokinetics of miglustat, an inhibitor of glucosylceramide synthase. J. Clin. Pharmacol. 47 (2007) 1277-1282
43. van Helvoort A., Smith A.J., Sprong H., Fritzsche I., Schinkel A.H., Borst P., and van Meer G. MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine. Cell 87 (1996) 507-517
44. Veldman R.J., Mita A., Cuvillier O., Garcia V., Klappe K., Medin J.A., Campbell J.D., Carpentier S., Kok J.W., and Levade T. The absence of functional glucosylceramide synthase does not sensitize melanoma cells for anticancer drugs. FASEB J. 17 (2003) 1144-1146
45. Wagner S.D., and Cwynarski K. Chronic lymphocytic leukaemia: new biological markers for assessing prognosis. Hematol. J. 5 (2004) 197-201
46. Wishart G.C., Bissett D., Paul J., Jodrell D., Harnett A., Habeshaw T., Kerr D.J., Macham M.A., Soukop M., and Leonard R.C. Quinidine as a resistance modulator of epirubicin in advanced breast cancer: mature results of a placebo-controlled randomized trial. J. Clin. Oncol. 12 (1994) 1771-1777
47. Yusa K., and Tsuruo T. Reversal mechanism of multidrug resistance by verapamil: direct binding of verapamil to P-glycoprotein on specific sites and transport of verapamil outward across the plasma membrane of K562/ADM cells. Cancer Res. 49 (1989) 5002-5006