title: The activity of atorvastatin and rosiglitazone on CD38, ZAP70 and apoptosis in lymphocytes of B-cell chronic lymphocytic leukemia in vitro.
abstract: 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/mm(3); leukocyte count: 50,500 ± 38,700/mm(3); and lymphocyte count: 45,700 ± 38,100/mm(3). 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.
authors.affiliation: Division of Hematology, Adnan Menderes University Medical Faculty, Aydin, Turkey. dr_yavas@yahoo.com
authors.forename: Irfan
authors.initials: I
authors.lastname: Yavasoglu
authors.forename: Gokhan
authors.initials: G
authors.lastname: Sargin
authors.forename: Gurhan
authors.initials: G
authors.lastname: Kadikoylu
authors.forename: Aslihan
authors.initials: A
authors.lastname: Karul
authors.forename: Zahit
authors.initials: Z
authors.lastname: Bolaman
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism*; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D000069059:Atorvastatin; D018956:CD5 Antigens / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism*
chemical_list: D017304:Annexin A5; D018956:CD5 Antigens; D006538:Heptanoic Acids; D019253:Proto-Oncogene Proteins c-bcl-2; D011758:Pyrroles; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000069059:Atorvastatin; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D051997:ADP-ribosyl Cyclase 1; D002118:Calcium