The activity of atorvastatin and rosiglitazone on CD38, ZAP70 and apoptosis in lymphocytes of B-cell chronic lymphocytic leukemia in vitro
详细信息    查看全文
  • 作者:Irfan Yavasoglu (1)
    Gokhan Sargin (2)
    Gurhan Kadikoylu (1)
    Aslihan Karul (3)
    Zahit Bolaman (1)
  • 关键词:Chronic lymphocytic leukemia ; Apoptosis ; In vitro
  • 刊名:Medical Oncology
  • 出版年:2013
  • 出版时间:September 2013
  • 年:2013
  • 卷:30
  • 期:3
  • 全文大小:307KB
  • 参考文献:1. Johston JB, Seftel M, Gibson SB. Chronic lymphocytic leukemia. In: Greer JP, Foerster J, Rodgers GM, Paraskevas F, Glader B, Arber DA, Means RT, editors. Wintrobe’s clinical hematology. 12th ed. Philadolphia: Lippincott Williams andWilkins; 2009. p. 2214-5.
    2. Chapman-Shimshoni D, Yuklea M, Shapiro H, Lishner M. Simvastatin induces apoptosis of B-CLL cells by activation of mitochondrial caspase 9. Exp Hematol. 2003;31:779-3. CrossRef
    3. Vitols S, Angelin B, Juliusson G. Simvastatin impairs mitogen-induced proliferation of malignant B-lymphocytes from humans-in vitro and in vivo studies. Lipids. 1997;32:255-2. CrossRef
    4. Padilla J, Kaur K, Cao HJ, Smith TJ, Phipps RP. Peroxisomeproliferator activator receptor-γ agonists and 15-deoxy-D12,14-PGJ2 induce apoptosis in normal and malignant B-lineage cells. J Immunol. 2000;165:6941-.
    5. Padilla J, Leung E, Phipps RP. Human B lymphocytes and B lymphomas express PPAR-γ and are killed by PPAR-γ agonists. Clin Immunol. 2002;103:22-3. CrossRef
    6. Jo SH, Yang C, Miao Q, Marzec M, Wasik MA, Lu P, et al. Peroxisome proliferator-activated receptor gamma promotes lymphocyte survival through its actions on cellular metabolic activities. J Immunol. 2006;177:3737-5.
    7. Wong WW, Dimitroulakos J, Minden MD, Penn LZ. HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis. Leukemia. 2002;16:508-9. CrossRef
    8. Cheson BD, Bennett JM, Grever M, Kay N, Keating MJ, O’Brien S, et al. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996;87:4990-.
    9. Panayiotidis P, Ganeshguru K, Jabbar SAB, Hoffbrand AV. Interleukin-4 inhibits apoptotic cell death and loss of the bcl-2 protein in B-chronic lymphocytic leukemia cells in vitro. Br J Heamatol. 1993;85:439. CrossRef
    10. Mainou-Fowler T, Craig VA, Copplestone AJ, Hamon MD, Prentice AG. Effect of anti-APO1 on spontaneous apoptosis of B cells in chronic lymphocytic leukaemia: the role of bcl-2 and interleukin-4. Leuk Lymphoma. 1995;19:301-. CrossRef
    11. Binet JL, Auquier A, Dighiero G, Chastang C, Piguet H, Goasguen J, et al. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer. 1981;48:198-06. CrossRef
    12. Ertault-Daneshpouy M, Noguera ME, Gisselbrecht C, Haddad A, Brice P, Marolleau JP, et al. ZAP-70 protein expression and CD38 positivity in B-cell chronic lymphocytic leukemia. Clin Adv Hematol Oncol. 2008;6:55-3.
    13. Lawen A. Apoptosis-an introduction. BioEssays. 2003;25:888-6. CrossRef
    14. Sanz L, Garcia-Marco JA, Casanova B, de La Fuente MT, Garcia-Gila M, Garcia-Pardo A, et al. Bcl-2 family gene modulation during spontaneous apoptosis of B-chronic lymphocytic leukemia cells. Biochem Biophys Res Commun. 2004;315:562-. CrossRef
    15. Kitada S, Andersen J, Akar S, Zapata JM, Takayama S, Krajewski S, et al. Expression of apoptosis-regulating proteins in chronic lymphocytic leukemia: correlations with in vitro and in vivo chemoresponses. Blood. 1998;91:3379-9.
    16. Saxena A, Viswanathan S, Moshynska O, Tandon P, Sankaran K, Sheridan DP. Mcl-1 and Bcl-2/Bax ratio are associated with treatment response but not with Rai stage in B-cell chronic lymphocytic leukemia. Am J Hematol. 2004;75:22-3. CrossRef
    17. Konopleva M, Elstner E, McQueen T, Tsao T, Sudarikov A, Hu W, et al. Peroxisome proliferator-activated receptor; and retinoid Xreceptor ligands are potent inducers of differentiation and apoptosis in leukemias. Mol Cancer Ther. 2004;3:1249-2.
    18. Gardner OS, Shiau CW, Chen CS, Graves LM. Peroxisome proliferator-activated receptor gamma-independent activation of p38 MAPK by thiazolidinediones involves calcium/calmodulin-dependent protein kinase II and protein kinase R: correlation with endoplasmic reticulum stress. J Biol Chem. 2005;280:10109-8. CrossRef
    19. Eucker J, Bangeroth K, Zavrski I, Krebbel H, Zang C, Heider U, et al. Ligands of peroxisome proliferator-activated receptor gamma induce apoptosis in multiple myeloma. Anticancer Drugs. 2004;15:955-0. CrossRef
    20. Groves MJ, Maccallum S, Boylan MT, Coates PJ, Tauro S. The annexin-V assay reflects susceptibility to in vitro membrane damage in chronic lymphocytic leukemia and may overestimate cell death. Am J Hematol. 2009;84:196-. CrossRef
    21. Castejón R, Yebra M, Citores MJ, Villarreal M, García-Marco JA, Vargas JA. Drug induction apoptosis assay as predictive value of chemotherapy response in patients with B-cell chronic lymphocytic leukemia. Leuk Lymphoma. 2009;50:593-03. CrossRef
    22. Spady DK, Dietschy JM. Sterol synthesis in vivo in 18 tissues of the squirrel monkey, guinea pig, rabbit, hamster, and rat. J Lipid Res. 1983;24:303-5.
    23. Simons K, Ikonen E. Functional lipid rafts in cell membranes. Nature. 1997;387:569-2. CrossRef
    24. Robinson MJ, Cheng M, Khokhlatchev A, Ebert D, Ahn N, Guan KL, et al. Contributions of the mitogen-activated protein (MAP) kinase backbone and phosphorylation loop to MEK specificity. J Biol Chem. 1996;271:29734-. CrossRef
    25. O’Donnell MP, Kasiske BL, Massy ZA, Guijarro C, Swan SK, Keane WF. Isoprenoids and Ras: potential role in chronic rejection. Kidney Int. 1995;52:29-3.
    26. Kwak B, Mulhaupt F, Myit S, Mach F. Statins as newly recognized type of immunomodulator. Nat Med. 2000;12:1399-02.
    27. Brumeanu TD, Goldstein R, Casares S. Down-regulation of autoreactive T-cells by HMG CoA reductase inhibitors. Clin Immunol. 2006;119:1-2. CrossRef
    28. Hillyard DZ, Cameron AJ, McIntyre AH, Hadden MH, Marshall HE, Johnston N, et al. Inhibition of proliferation and signalling mechanisms in human lymphocytes by fluvastatin. Clin Exp Pharmacol Physiol. 2002;8:673-. CrossRef
    29. Fehr T, Kahlert C, Fierz W, Joller-Jemelka HI, Riesen WF, Rickli H, et al. Statin-induced immunomodulatory effects on human T cells in vivo. Atherosclerosis. 2004;175:83-0. CrossRef
    30. Branco-Colio LM, Munoz-Garcia B, Martin-Ventura JL, Lorz C, Diaz C, Hernandez G, et al. 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors decrease Fas ligand expression and cytotoxicity in activated human T lymphocytes. Circulation. 2003;108:1506-3. CrossRef
    31. Lawman S, Mauri C, Jury EC, Cook HT, Ehrenstein MR. Atorvastatin inhibits autoreactive B cell activation and delays lupus development in New Zealand Black/White F1 mice. J Immunol. 2004;173:7641-.
    32. Ajith TA, Soja M. A comparative study on the antimutagenicity of atorvastatin and lovastatin against directly acting mutagens. Cell Biol Toxicol. 2006;22:269-4. CrossRef
    33. Ajith TA, Harikumar KB, Thasna H, Sabu MC, Babitha NV. Proapoptotic and antitumor activities of the HMG-CoA reductase inhibitor, lovastatin, against Dalton’s lymphoma ascites tumor in mice. Clin Chim Acta. 2006;366:322-. CrossRef
    34. Ajith TA, Anu V, Riji T. Antitumor and apoptosis promoting properties of atorvastatin, an inhibitor of HMG-CoA reductase, against Dalton’s Lymphoma Ascites tumor in mice. J Exp Ther Oncol. 2008;7:291-.
    35. Ajith TA, Riji T, Anu V. In vitro anti-oxidant and DNA protective effects of the novel 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor rosuvastatin. Clin Exp Pharmacol Physiol. 2008;35:625-. CrossRef
    36. Podhorecka M, Halicka D, Klimek P, Kowal M, Chocholska S, Dmoszynska A. Simvastatin and purine analogs have a synergic effect on apoptosis of chronic lymphocytic leukemia cells. Ann Hematol. 2010;89:1115-4. CrossRef
    37. Drake DR, Braciale TJ. Cutting edge: lipid rafts integrity affects the efficiency of MHC class I tetramer binding and cell surface TCR arrangement on CD8?+?T cells. J Immunol. 2001;166:7009-3.
    38. Cheng PC, Dykstra ML, Michell RN, Pierce SK. A role of lipid rafts in B cell antigen receptor signaling and antigen targeting. J Exp Med. 1999;190:1549-0. CrossRef
    39. Xavier R, Brennan T, Li Q, McCormack C, Seed B. Membrane compartmentation is required for efficient T cell activation. Immunity. 1998;8:723-2. CrossRef
    40. Sarrabayrouse G, Synaeve C, Leveque K, Favre G, Tilkin-Mariamé AF. Statins stimulate in vitro membrane FasL expression and lymphocyte apoptosis through RhoA/ROCK pathway in murine melanoma cells. Neoplasia. 2007;9:1078-0. CrossRef
    41. Tomiyama N, Yasuda N, Iwano C, Matzno S, Matsuyama K. Flow cytometric evaluation of synergistic pro-apoptotic effects of statins and clofibrates in IM-9 human lymphoblasts. Clin Exp Pharmacol Physiol. 2007;34:876-0. CrossRef
    42. Gajski G, Garaj-Vrhovac V, Orescanin V. Cytogenetic status and oxidative DNA-damage induced by atorvastatin in human peripheral blood lymphocytes: standard and Fpg-modified comet assay. Toxicol Appl Pharmacol. 2008;231:85-3. CrossRef
    43. Cafforio P, Dammacco F, Gernone A, Silvestris F. Statins activate the mitochondrial pathway of apoptosis in human lymphoblasts and myeloma cells. Carcinogenesis. 2005;26:883-1. CrossRef
    44. Blank N, Schiller M, Krienke S, Busse F, Sch?tz B, Ho AD, et al. Atorvastatin inhibits T cell activation through 3-hydroxy-3-methylglutaryl coenzyme A reductase without decreasing cholesterol synthesis. J Immunol. 2007;179:3613-1.
    45. Ray DM, Akbiyik F, Phipps RP. The peroxisome proliferator-activated receptor gamma (PPARgamma) ligands 15-deoxy-Delta12,14-prostaglandin J2 and ciglitazone induce human B lymphocyte and B cell lymphoma apoptosis by PPARgamma-independent mechanisms. J Immunol. 2006;177:5068-6.
    46. Liu JJ, Liu PQ, Lin DJ, Xiao RZ, Huang M, Li XD, et al. Down regulation of cyclooxygenase-2 expression and activation of caspase-3 are involved in peroxisome proliferator-activated receptor-gamma agonists induced apoptosis in human monocyte leukemia cells in vitro. Ann Hematol. 2007;86:173-3. CrossRef
    47. Bairey O, Vanichkin A, Shpilberg O. Arsenic-trioxide-induced apoptosis of chronic lymphocytic leukemia cells. Int J Lab Hematol. 2010;32:77-5. CrossRef
    48. Boelens J, Lust S, Van Bockstaele F, Van Gele M, Janssens A, Derycke L, et al. Steroid effects on ZAP-70 and SYK in relation to apoptosis in poor prognosis chronic lymphocytic leukemia. Leuk Res. 2009;33:1335-3. CrossRef
  • 作者单位:Irfan Yavasoglu (1)
    Gokhan Sargin (2)
    Gurhan Kadikoylu (1)
    Aslihan Karul (3)
    Zahit Bolaman (1)

    1. Division of Hematology, Adnan Menderes University Medical Faculty, Aydin, Turkey
    2. Department of Internal Medicine, Adnan Menderes University Medical Faculty, Aydin, Turkey
    3. Department of Biochemistry, Adnan Menderes University Medical Faculty, Aydin, Turkey
文摘
There are a number of studies about the effects of statins and thiazolidinediones on lymphocytes. However, there is no study about possible effects of atorvastatin and rosiglitazone on lymphocytes in patients with chronic lymphocytic leukemia (CLL). We aimed to investigate the effects of atorvastatin and rosiglitazone on CD38, ZAP-70, Annexin V and bcl-2 in lymphocytes of CLL in vitro. Seven (4 males and 3 females) patients with CLL with average age of 56?±?8?years were enrolled to the study. The mean values of laboratory tests were as follows: hemoglobin: 12?±?1.8?g/dl; hematocrit:?%35?±?6; platelet count: 156,000?±?68,000/mm3; leukocyte count: 50,500?±?38,700/mm3; and lymphocyte count: 45,700?±?38,100/mm3. The study was performed in three cell cultures groups. Mononuclear cells of blood samples from peripheral veins were separated by Ficoll method. On culture plate with 24 wells, it was suspended with 2?ml RPMI 1640. Then, the plates were incubated in ?%5 CO2 at 37?°C for 24?h. 5?μM atorvastatin-calcium was given to first group, 2?μM rosiglitazone maleate was given to second group, and the third group was included in the study as control group. After 24?h, the expressions of CD5, CD38, ZAP-70 and Annexin V by using flow cytometry with EPICS XL-MCL and the levels of bcl-2 by using ELISA method were re-evaluated. Two-paired Student's t test was used for comparison of the results, and p?<?0.05 was accepted as a significance level. While atorvastatin and rosiglitazone did not affect the expression of CD38 and the level of bcl-2, these drugs significantly increased the level of Annexin V when compared with control group (p?<?0.001). Both drugs significantly decreased the expressions of CD5 (p?=?0.03) and ZAP-70 (p?<?0.05) compared with control group. Atorvastatin and rosiglitazone increased apoptosis in lymphocytes of CLL in vitro. Moreover, these drugs decreased the expressions of CD5 and ZAP-70. These drugs must be studied in more detail in the pathogenesis and treatment for CLL.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700