Inhibition of PDE3, PDE4 and PDE7 potentiates glucocorticoid-induced apoptosis and overcomes glucocorticoid resistance in CEM T leukemic cells

Biochemical Pharmacology

Volumn 79, Issue 3, 2010, Pages 321-329

  Dong, Hongli ^a   Zitt, Christof ^b   Auriga, Cornelia ^b   Hatzelmann, Armin ^b   Epstein, Paul M ^a  

^a UNIVERSITY OF CONNECTICUT HEALTH CENTER   (United States)

^b Nycomed GmbH   (Germany)

Author keywords

cAMP; Glucocorticoids; Leukemia; Phosphodiesterase

Indexed keywords

8' CHLORO 6' [4 [(4 METHYLPIPERAZIN 1 YL)CARBONYL]PHENYL] 1'H SPIRO[CYCLOHEXANE 1,4' QUINAZOLIN] 2'(3'H) ONE; DIPYRIDAMOLE; GLUCOCORTICOID; HYDROCORTISONE; ISOBUTYLMETHYLXANTHINE; MILRINONE; MOTAPIZONE; PHOSPHODIESTERASE III; PHOSPHODIESTERASE III INHIBITOR; PHOSPHODIESTERASE IIIB; PHOSPHODIESTERASE INHIBITOR; PHOSPHODIESTERASE IV; PHOSPHODIESTERASE IV INHIBITOR; PHOSPHODIESTERASE IVA; PHOSPHODIESTERASE IVD; PHOSPHODIESTERASE VII; PHOSPHODIESTERASE VII INHIBITOR; PHOSPHODIESTERASE VIIA; PHOSPHODIESTERASE VIIIA; PICLAMILAST; ROLIPRAM; SPIROQUINAZOLINONE; UNCLASSIFIED DRUG; ZARDAVERINE;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER RESISTANCE; CELL VIABILITY; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG EFFECT; DRUG MECHANISM; DRUG POTENTIATION; ENZYME INHIBITION; HUMAN; HUMAN CELL; LEUKEMIA CELL; LEUKEMIA CELL LINE; PRIORITY JOURNAL; PROTEIN EXPRESSION;

APOPTOSIS; CYCLIC NUCLEOTIDE PHOSPHODIESTERASES, TYPE 3; CYCLIC NUCLEOTIDE PHOSPHODIESTERASES, TYPE 4; CYCLIC NUCLEOTIDE PHOSPHODIESTERASES, TYPE 7; DRUG RESISTANCE, NEOPLASM; DRUG SYNERGISM; GLUCOCORTICOIDS; HUMANS; JURKAT CELLS; LEUKEMIA, T-CELL; PHOSPHODIESTERASE INHIBITORS; TUMOR CELLS, CULTURED;

EID: 70449656971     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bcp.2009.09.001     Document Type: Article

References (44)

1. Lerner A., and Epstein P.M. Cyclic nucleotide phosphodiesterases as targets for treatment of haematological malignancies. Biochem J 393 (2006) 21-41
2. Ogawa R., Streiff M.B., Bugayenko A., and Kato G.J. Inhibition of PDE4 phosphodiesterase activity induces growth suppression, apoptosis, glucocorticoid sensitivity, p53, and p21(WAF1/CIP1) proteins in human acute lymphoblastic leukemia cells. Blood 99 (2002) 3390-3397
3. Tiwari S., Dong H., Kim E.J., Weintraub L., Epstein P.M., and Lerner A. Type 4 cAMP phosphodiesterase (PDE4) inhibitors augment glucocorticoid-mediated apoptosis in B cell chronic lymphocytic leukemia (B-CLL) in the absence of exogenous adenylyl cyclase stimulation. Biochem Pharmacol 69 (2005) 473-483
4. Ploner C., Schmidt S., Presul E., Renner K., Schrocksnadel K., Rainer J., et al. Glucocorticoid-induced apoptosis and glucocorticoid resistance in acute lymphoblastic leukemia. J Steroid Biochem Mol Biol 93 (2005) 153-160
5. Tenor H., Staniciu L., Schudt C., Hatzelmann A., Wendel A., Djukanovic R., et al. Cyclic nucleotide phosphodiesterases from purified human CD4+ and CD8+ T lymphocytes. Clin Exp Allergy 25 (1995) 616-624
6. Giembycz M.A., Corrigan C.J., Seybold J., Newton R., and Barnes P.J. Identification of cyclic AMP phosphodiesterases 3, 4 and 7 in human CD4+ and CD8+ T-lymphocytes: role in regulating proliferation and the biosynthesis of interleukin-2. Br J Pharmacol 118 (1996) 1945-1958
7. Kim D.H., and Lerner A. Type 4 cyclic adenosine monophosphate phosphodiesterase as a therapeutic target in chronic lymphocytic leukemia. Blood 92 (1998) 2484-2494
8. Siegmund B., Welsch J., Loher F., Meinhardt G., Emmerich B., Endres S., et al. Phosphodiesterase type 4 inhibitor suppresses expression of anti-apoptotic members of the Bcl-2 family in B-CLL cells and induces caspase-dependent apoptosis. Leukemia 15 (2001) 1564-1571
9. Moon E., Lee R., Near R., Weintraub L., Wolda S., and Lerner A. Inhibition of PDE3B augments PDE4 inhibitor-induced apoptosis in a subset of patients with chronic lymphocytic leukemia. Clin Cancer Res 8 (2002) 589-595
10. Lee R., Wolda S., Moon E., Esselstyn J., Hertel C., and Lerner A. PDE7A is expressed in human B-lymphocytes and is up-regulated by elevation of intracellular cAMP. Cell Signal 14 (2002) 277-284
11. Li L., Yee C., and Beavo J.A. CD3- and CD28-dependent induction of PDE7 required for T cell activation. Science 283 (1999) 848-851
12. Yang G., McIntyre K.W., Townsend R.M., Shen H.H., Pitts W.J., Dodd J.H., et al. Phosphodiesterase 7A-deficient mice have functional T cells. J Immunol 171 (2003) 6414-6420
13. Nueda A., Garcia-Roger N., Domenech T., Godessart N., Cardenas A., Santamaria-Babi L.F., et al. Phosphodiesterase 7A1 is expressed in human CD4+ naive T cells at higher levels than in CD4+ memory cells and is not required during their CD3/CD28-dependent activation. Cell Immunol 242 (2006) 31-38
14. Smith S.J., Cieslinski L.B., Newton R., Donnelly L.E., Fenwick P.S., Nicholson A.G., et al. Discovery of BRL 50481 [3-(N,N-dimethylsulfonamido)-4-methyl-nitrobenzene], a selective inhibitor of phosphodiesterase 7: in vitro studies in human monocytes, lung macrophages, and CD8+ T-lymphocytes. Mol Pharmacol 66 (2004) 1679-1689
15. Bloom T.J., and Beavo J.A. Identification and tissue-specific expression of PDE7 phosphodiesterase splice variants. Proc Natl Acad Sci USA 93 (1996) 14188-14192
16. Smith S.J., Brookes-Fazakerley S., Donnelly L.E., Barnes P.J., Barnette M.S., and Giembycz M.A. Ubiquitous expression of phosphodiesterase 7A in human proinflammatory and immune cells. Am J Physiol Lung Cell Mol Physiol 284 (2003) L279-L289
17. Hetman J.M., Soderling S.H., Glavas N.A., and Beavo J.A. Cloning and characterization of PDE7B, a cAMP-specific phosphodiesterase. Proc Natl Acad Sci USA 97 (2000) 472-476
18. Gardner C., Robas N., Cawkill D., and Fidock M. Cloning and characterization of the human and mouse PDE7B, a novel cAMP-specific cyclic nucleotide phosphodiesterase. Biochem Biophys Res Commun 272 (2000) 186-192
19. Zhang L., Murray F., Zahno A., Kanter J.R., Chou D., Suda R., et al. Cyclic nucleotide phosphodiesterase profiling reveals increased expression of phosphodiesterase 7B in chronic lymphocytic leukaemia. Proc Natl Acad Sci USA 105 (2008) 19532-19537
20. Seybold J., Thomas D., Witzenrath M., Boral S., Hocke A.C., Burger A., et al. Tumor necrosis factor-alpha-dependent expression of phosphodiesterase 2: role in endothelial hyperpermeability. Blood 105 (2005) 3569-3576
21. Lorthiois E., Bernardelli P., Vergne F., Oliveira C., Mafroud A.K., Proust E., et al. Spiroquinazolinones as novel, potent, and selective PDE7 inhibitors. Part 1. Bioorg Med Chem Lett 14 (2004) 4623-4626
22. Tenor H., Hedbom E., Hauselmann H.J., Schudt C., and Hatzelmann A. Phosphodiesterase isoenzyme families in human osteoarthritis chondrocytes-functional importance of phosphodiesterase 4. Br J Pharmacol 135 (2002) 609-618
23. Soderling S.H., Bayuga S.J., and Beavo J.A. Cloning and characterization of a cAMP-specific cyclic nucleotide phosphodiesterase. Proc Natl Acad Sci USA 95 (1998) 8991-8996
24. Fisher D.A., Smith J.F., Pillar J.S., St Denis S.H., and Cheng J.B. Isolation and characterization of PDE8A, a novel human cAMP-specific phosphodiesterase. Biochem Biophys Res Commun 246 (1998) 570-577
25. Gamanuma M., Yuasa K., Sasaki T., Sakurai N., Kotera J., and Omori K. Comparison of enzymatic characterization and gene organization of cyclic nucleotide phosphodiesterase 8 family in humans. Cell Signal 15 (2003) 565-574
26. Hoffmann R., Wilkinson I.R., McCallum J.F., Engels P., and Houslay M.D. cAMP-specific phosphodiesterase HSPDE4D3 mutants which mimic activation and changes in rolipram inhibition triggered by protein kinase A phosphorylation of Ser-54: generation of a molecular model. Biochem J 333 Pt 1 (1998) 139-149
27. Gantner F., Gotz C., Gekeler V., Schudt C., Wendel A., and Hatzelmann A. Phosphodiesterase profile of human B lymphocytes from normal and atopic donors and the effects of PDE inhibition on B cell proliferation. Br J Pharmacol 123 (1998) 1031-1038
28. Glavas N.A., Ostenson C., Schaefer J.B., Vasta V., and Beavo J.A. T cell activation up-regulates cyclic nucleotide phosphodiesterases 8A1 and 7A3. Proc Natl Acad Sci USA 98 (2001) 6319-6324
29. Dong H., Osmanova V., Epstein P.M., and Brocke S. Phosphodiesterase 8 (PDE8) regulates chemotaxis of activated lymphocytes. Biochem Biophys Res Commun 345 (2006) 713-719
30. Jiang X., Paskind M., Weltzien R., and Epstein P.M. Expression and regulation of mRNA for distinct isoforms of cAMP-specific PDE-4 in mitogen-stimulated and leukemic human lymphocytes. Cell Biochem Biophys 28 (1998) 135-160
31. Gantner F., Tenor H., Gekeler V., Schudt C., Wendel A., and Hatzelmann A. Phosphodiesterase profiles of highly purified human peripheral blood leukocyte populations from normal and atopic individuals: a comparative study. J Allergy Clin Immunol 100 (1997) 527-535
32. Peter D., Jin S.L., Conti M., Hatzelmann A., and Zitt C. Differential expression and function of phosphodiesterase 4 (PDE4) subtypes in human primary CD4+ T cells: predominant role of PDE4D. J Immunol 178 (2007) 4820-4831
33. Erdogan S., and Houslay M.D. Challenge of human Jurkat T-cells with the adenylate cyclase activator forskolin elicits major changes in cAMP phosphodiesterase (PDE) expression by up-regulating PDE3 and inducing PDE4D1 and PDE4D2 splice variants as well as down-regulating a novel PDE4A splice variant. Biochem J 321 Pt 1 (1997) 165-175
34. Seybold J., Newton R., Wright L., Finney P.A., Suttorp N., Barnes P.J., et al. Induction of phosphodiesterases 3B, 4A4, 4D1, 4D2, and 4D3 in Jurkat T-cells and in human peripheral blood T-lymphocytes by 8-bromo-cAMP and Gs-coupled receptor agonists. Potential role in beta2-adrenoreceptor desensitization. J Biol Chem 273 (1998) 20575-20588
35. Giembycz M.A., and Smith S.J. Phosphodiesterase 7 (PDE7) as a therapeutic target. Drugs Future 31 (2006) 207-229
36. Nakata A., Ogawa K., Sasaki T., Koyama N., Wada K., Kotera J., et al. Potential role of phosphodiesterase 7 in human T cell function: comparative effects of two phosphodiesterase inhibitors. Clin Exp Immunol 128 (2002) 460-466
37. Kadoshima-Yamaoka K., Murakawa M., Goto M., Tanaka Y., Inoue H., Murafuji H., et al. ASB16165, a novel inhibitor for phosphodiesterase 7A (PDE7A), suppresses IL-12-induced IFN-gamma production by mouse activated T lymphocytes. Immunol Lett 122 (2009) 193-197
38. Fortin M., D'Anjou H., Higgins M.E., Gougeon J., Aube P., Moktefi K., et al. A multi-target antisense approach against PDE4 and PDE7 reduces smoke-induced lung inflammation in mice. Respir Res 10 (2009) 39
39. Giembycz M.A. Can the anti-inflammatory potential of PDE4 inhibitors be realized: guarded optimism or wishful thinking?. Br J Pharmacol 155 (2008) 288-290
40. Spina D. PDE4 inhibitors: current status. Br J Pharmacol 155 (2008) 308-315
41. Jiang X., Li J., Paskind M., and Epstein P.M. Inhibition of calmodulin-dependent phosphodiesterase induces apoptosis in human leukemic cells. Proc Natl Acad Sci USA 93 (1996) 11236-11241
42. Epstein P.M. Antisense inhibition of phosphodiesterase expression. Methods 14 (1998) 21-33
43. Meyers J.A., Su D.W., and Lerner A. Chronic lymphocytic leukemia and B and T cells differ in their response to cyclic nucleotide phosphodiesterase inhibitors. J Immunol 182 (2009) 5400-5411
44. Livak K.J., and Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25 (2001) 402-408