RESEARCH PAPER
Hematological effects of protein kinases inhibitor maleimide derivative (1-(4 -Cl-benzyl)-3-Cl-4-(CF3-phenylamino)-1H-pyrrole-2,5-dione)
 
More details
Hide details
1
Department of Cytophysiology, Taras Shevchenko National University, Kiev, Ukraine
 
2
Department of Hematology, Research Centre for Radiation Medicine Academy of Medical Science of Ukraine
 
 
Corresponding author
Iryna Byelinska   

Cytophysiology Department, Faculty of Biology, 2, Academician Glushkov Avenue, Building 12, Taras Shevchenko National University, Kiev, Ukraine.
 
 
J Pre Clin Clin Res. 2010;4(1):32-35
 
KEYWORDS
ABSTRACT
Maleimide derivative (MD, 1-(4 -Cl-benzyl)-3-Cl-4-(CF3-phenylamino)-1Н-pyrrole-2,5-dione) is an inhibitor of a number of protein kinases and proliferative activity of tumour cells. A study of potential anticancer drug effects on different systems of the organism, including the hemopoietic system, is an urgent issue. The aim of the present study was to investigate MD eff ects on rat blood cells parameters. It was found that daily treatment with MD for 25 days (2.7, 0.027, 0.00027 mg/kg) does not signifi cantly affect the erythroid parameters of rats. However, MD at 2.7 and 0.027 mg/kg slightly increased and at 0.00027 mg/kg decreased the erythrocytes mean volume. MD at 0.00027 mg/kg did not affect the number of blood leukocytes. MD at 2.7 and 0.027 mg/kg reduced the leukocytes count by decreasing the absolute number of the neutrophylic and eosinophylic granulocytes and monocytes. Thus, the MD-induced effects on the erythrocytes and thrombocytes parameters do not restrict its application as an antitumor drug in indicated doses. However, it is necessary to control the leukocytes count to detect the occurrence of leukopenia during MD therapy.
 
REFERENCES (22)
1.
Novak K: Conference report – Protein kinase inhibitors in Cancer – Mixing and Matching. Med Gen Med 2004, 6, 23.
 
2.
Zeng Z, Samudio IS, Zhang W, Estrov Z, Pelicano H, Harris D, Frolova O, Hail N, Chen W, Kornblau SM, Huang P, Lu Y, Mills GM, Andreeff M, Konopleva M: Simultaneous Inhibition of PDK1/AKT and Fms- Like tyrosine kinase 3 signaling by a small-molecule KP372-1 induces mitochondrial dysfunction and Apoptosis in Acute myelogeneous leukemia. Cancr Res 2006, 66, 3737-3746.
 
3.
Dubinina GG, Chupryna OO, Platonov MO, Borysko PO, Ostrovska GV, Tolmachov AO, Shtil AA: In Silico design of protein kinase inhibitors: successes and failures. Anticancer Agents Med Chem 2007, 7, 171-188.
 
4.
Dubinina GG, Volovenko YuM: Compound of 1,4-disubstituted 5- amino-1,2-dihydropyrrole-3-one having anticancer activity. Pat. 22204 (UA), 21.02.2006. Appl. U200601855. 25.04.2007.
 
5.
Dubinina GG, Golovach SM, Kozlovsky VO, Tolmachov AO, Volovenko YuM: Antiproliferative activity of the new derivatives of 1-(4-R-benzyl)- 3-R1-4-(R2-phenylamino)-1<-pyrrole-2,5-dione. Journal Organichnoi ta farmacevtichnoi khimii (Ukraine) 2007, 5, 39-49.
 
6.
Bone HK, Welham MJ: Phosphoinositide 3-kinase signalling regulates early development and developmental haemopoiesis. J Cell Sci 2007, 120, 1752-1762.
 
7.
Shrivastav A, Varma S, Lawman Z, Yang SH, Ritchie SA, Bonham K, Singh SM, Saxena A, Sharma RK: Requirement of N-myristoyltransferase 1 in the development of monocytic lineage. J Immunol 2008, 180, 1019-1028.
 
8.
Rane SG, Reddy EP: JAKs, STATs and Src kinases in hematopoiesis. Oncogene 2002, 21, P. 3334-3358.
 
9.
King MJ, Smythe JS, Mushens R: Eosin-5-maleimide binding to band 3 and Rh-related proteins forms the basis of a screening test for hereditary spherocytosis. Biochem Biophys Res Commun 2003, 312, 467-472.
 
10.
Kedar PS, Colah RB, Kulkarni SE, Ghosh K, Mohanty D: Expe rien ce with eosin-5-maleimide as a diagnostic tool for red cell membrane cytoskeleton disorders. Bioconjug Chem 2003, 14, 1253-1259.
 
11.
Yang KJ, Shin S, Piao L, Shin E, Li Y, Ah Park K, Byun HS, Won M, Hong J, Kweon GR, Hur GM, Seok JH, Chun T, Brazil DP, Hemmings BA, Park J: Regulation of 3-phosphoinositide-dependent protein kinase- 1 (PDK1) by Src involves tyrosine phosphorylation of PDK1 and Src SH2 domain binding. J Biol Chem 2008, 283, 1480 1491.
 
12.
De Jong K, Rettig MP, Low PS, Kuypers FA: Protein kinase C activation induces phosphatidylserine exposure on red blood cells. Biochemistry 2002, 41, 12562-12567.
 
13.
Niemoeller OM, Bentzen PJ, Lang E, Lang F: Adenosine protects against suicidal erythrocyte death. Pfl ugers Arch 2007, 454, 427-439.
 
14.
Klarl BA, Lang PA, Kempe DS: Protein kinase C mediates erythrocyte ‘programmed cell death’ following glucose depletion. Am J Physiol Cell Physiol 2006, 290, C244-C253.
 
15.
Lutz MA, Correll PH: Activation of CR3-mediated phagocytosis by MSP requires the RON receptor, tyrosine kinase activity, phosphatidylinositol 3-kinase, and protein kinase C zeta. J Leukoc Biol 2003, 73, 802-814.
 
16.
Wang JP: Characterizadtion of maliemide-activated Ca2+ entry in neutrophils. Biochem Pharmacol 2003, 65, 1923-1929.
 
17.
Dewitt S, Hallett MB: Cytosolic free Ca2+ changes and calpain activation are required for < i ntegrin–accelerated phagocytosis by human neutrophils. J Cell Biol 2002, 159, 181–189.
 
18.
Tintinger G, Steel HC, Anderson R: Taming the neutrophil: calcium clearance and infl ux mechanisms as novel targets for pharmacological control. Clin Exp Immunol 2005, 141, 191–200.
 
19.
Sarantis H, Gray-Owen SD: The specifi c innate immune receptor CEACAM3 triggers neutrophil bactericidal activities via a Syk kinasedependent pathway. Cell Microbiol 2007, 9, 2167-2180.
 
20.
Fudala R, Krupa A, Matthay MA, Allen TC, Kurdowska AK: Anti-IL-8 autoantibody:IL-8 immune complexes suppress spontaneous apoptosis of neutrophils. Am J Physiol Lung Cell Mol Physiol 2007, 293, L364- 374.
 
21.
Pearn L, Fisher J, Burnett AK, Darley RL: The role of PKC and PDK1 in monocyte lineage specifi cation by Ras. Blood 2007, 109, 4461-4469.
 
22.
Ibrahim S, Calzada C, Pruneta-Deloche V, Lagarde M, Ponsin G: The transfer of VLDL-associated phospholipids to activated platelets depends upon cytosolic phospholipase A2 activity. J Lipid Res 2007, 48, 1533-1538.
 
eISSN:1898-7516
ISSN:1898-2395
Journals System - logo
Scroll to top