Experimental Hematology
Volume 30, Issue 10 , Pages 1107-1114 , October 2002

Plant cytokinin analogues with inhibitory activity on cyclin-dependent kinases exert their antiproliferative effect through induction of apoptosis initiated by the mitochondrial pathway: Determination by a multiparametric flow cytometric analysis

  • Katrien Vermeulen

      Affiliations

    • Laboratory of Experimental Hematology, University of Antwerp, Antwerp University Hospital, Edegem, Belgium
    • ,
  • Miroslav Strnad

      Affiliations

    • Laboratory of Growth Regulators, Institute of Experimental Botany ASCR and Palacký University, Olomouc, Czech Republic
    • ,
  • Libor Havlı́cěk

      Affiliations

    • Laboratory of Growth Regulators, Institute of Experimental Botany ASCR and Palacký University, Olomouc, Czech Republic
    • ,
  • Harry Van Onckelen

      Affiliations

    • Laboratory of Plant Physiology, Department of Biology, University of Antwerp, Wilrijk, Belgium
    • ,
  • Marc Lenjou

      Affiliations

    • Laboratory of Experimental Hematology, University of Antwerp, Antwerp University Hospital, Edegem, Belgium
    • ,
  • Griet Nijs

      Affiliations

    • Laboratory of Experimental Hematology, University of Antwerp, Antwerp University Hospital, Edegem, Belgium
    • ,
  • Dirk R Van Bockstaele

      Affiliations

    • Laboratory of Experimental Hematology, University of Antwerp, Antwerp University Hospital, Edegem, Belgium
    • ,
  • Zwi N Berneman

      Affiliations

    • Corresponding Author InformationOffprint requests to: Zwi N. Berneman, M.D., Ph. D., Laboratory of Experimental Hematology, University of Antwerp, Antwerp University Hospital, Wilrijkstraat 10, B-2650 Edegem, Belgium
    • Laboratory of Experimental Hematology, University of Antwerp, Antwerp University Hospital, Edegem, Belgium

Received 25 March 2002 ,Revised 24 May 2002 ,Accepted 17 June 2002.

References 

  1. Hall M, Peters G. Genetic alterations of cyclins, cyclin-dependent kinases, and CDK inhibitors in human cancer. Adv Cancer Res. 1996;68:67
  2. Sherr CJ. Cancer cell cycles. Science. 1996;274:1672
  3. Afford S, Randhawa S. Apoptosis. Mol Pathol. 2000;53:55
  4. Negoescu A. Apoptosis in cancer (Therapeutic implications). Histol Histopathol. 2000;15:281
  5. Schulze-Gahmen U, Brandsen J, Jones HD, et al.  Multiple modes of ligand recognition (Crystal structures of cyclin-dependent protein kinase 2 in complex with ATP and two inhibitors, olomoucine and isopentenyladenine). Proteins. 1995;22:378
  6. Rialet V, Meijer L. A new screening test for antimitotic compounds using the universal M phase-specific protein kinase, p34cdc2/cyclin Bcdc13, affinity-immobilized on p13suc1-coated microtitration plates. Anticancer Res. 1991;11:1581
  7. Vesely J, Havlicek L, Strnad M, et al.  Inhibition of cyclin- dependent kinases by purine analogues. Eur J Biochem. 1994;224:771
  8. De Azevedo WF, Leclerc S, Meijer L, Havlicek L, Strnad M, Kim SH. Inhibition of cyclin-dependent kinases by purine analogues (Crystal structure of human cdk2 complexed with roscovitine). Eur J Biochem. 1997;243:518
  9. Mani S, Wang CG, Wu KM, Francis R, Pestell R. Cyclin- dependent kinase inhibitors (Novel anticancer agents). Exp Opin Invest Drugs. 2000;9:1849
  10. Senderowicz AM, Sausville EA. Preclinical and clinical development of cyclin-dependent kinase modulators. J Natl Cancer Inst. 2000;92:376
  11. Vermeulen K, Strnad M, Krystof V, et al.  Antiproliferative effect on plant cytokinin analogues with an inhibitory activity on cyclin-dependent kinases. Leukemia. 2002;16:299
  12. Havlicek L, Hanus J, Vesely J, et al.  Cytokinin-derived cyclin-dependent kinase inhibitors (Synthesis and cdc2 inhibitory activity of olomoucine and related compounds). J Med Chem. 1997;40:408
  13. Villunger A, Egle A, Kos M, et al.  Drug-induced apoptosis is associated with enhanced Fas (Apo-1/CD95) ligand expression but occurs independently of Fas (Apo-1/CD95) signaling in human T-acute lymphatic leukemia cells. Cancer Res. 1997;57:3331
  14. Stewart CC, Steinkamp JA. Quantitation of cell concentration using the flow cytometer. Cytometry. 1982;2:238
  15. Schlenke P, Frohn C, Kluter H, et al.  Evaluation of a flow cytometric method for simultaneous leukocyte phenotyping and quantification by fluorescent microspheres. Cytometry. 1998;33:310
  16. Lizard G, Fournel S, Genestier L, et al.  Kinetics of plasma membrane and mitochondrial alterations in cells undergoing apoptosis. Cytometry. 1995;21:275
  17. Ellwart JW, Dormer P. Vitality measurement using spectrum shift in Hoechst 33342 stained cells. Cytometry. 1990;11:239
  18. Belloc F, Dumain P, Boisseau MR, et al.  A flow cytometric method using Hoechst 33342 and propidium iodide for simultaneous cell cycle analysis and apoptosis determination in unfixed cells. Cytometry. 1994;17:59
  19. Vial JP, Belloc F, Dumain P, et al.  Study of the apoptosis induced in vitro by antitumoral drugs on leukaemic cells. Leuk Res. 1997;21:163
  20. Castedo M, Hirsch T, Susin SA, et al.  Sequential acquisition of mitochondrial and plasma membrane alteration during early lymphocyte apoptosis. J Immunol. 1996;157:512
  21. Denecker G, Dooms H, Van Loo G, et al.  Phosphatidyl serine exposure during apoptosis precedes release of cytochrome c and decrease in mitochondrial transmembrane potential. FEBS Lett. 2000;465:47
  22. Green DR, Reed JC. Mitochondria and apoptosis. Science. 1998;281:1309
  23. Mancini M, Sedghinasab M, Knowlton K, Tam A, Hockenbery D, Anderson BO. Flow cytometric measurement of mitochondrial mass and function (A novel method for assessing chemoresistance). Ann Surg Oncol. 1998;5:287
  24. Rasola A, Geuna M. A flow cytometry assay simultaneously detects independent apoptotic parameters. Cytometry. 2001;45:151
  25. Garcia CM, Peterson EP, Leiting B, Ruel R, Nicholson DW, Thornberry NA. Inhibition of human caspases by peptide-based and macromolecular inhibitors. J Biol Chem. 1998;273:32608
  26. Ekert PG, Silke J, Vaux DL. Caspase inhibitors. Cell Death Differ. 1999;6:1081
  27. Schotte P, Declercq W, Van Huffel S, Vandenabeele P, Beyaert R. Non-specific effects of methyl ketone peptide inhibitors of caspases. FEBS Lett. 1999;442:117
  28. Sun XM, MacFarlane M, Zhuang J, Wolf BB, Green DR, Cohen GM. Distinct caspase cascades are initiated in receptor-mediated and chemical-induced apoptosis. J Biol Chem. 1999;274:5053
  29. Komoriya A, Packard BZ, Brown MJ, Wu ML, Henkart PA. Assessment of caspase activities in intact apoptotic thymocytes using cell-permeable fluorogenic caspase substrates. J Exp Med. 2000;191:1819
  30. Kroemer G, Zamzami N, Susin SA. Mitochondrial control of apoptosis. Immunol Today. 1997;18:44
  31. Salvioli S, Dobrucki J, Moretti L, et al.  Mitochondrial heterogeneity during staurosporine-induced apoptosis in HL60 cells (analysis at the single cell and single organelle level). Cytometry. 2000;40:189
  32. Bratton DL, Fadok VA, Richter DA, et al.  Polyamine regulation of plasma membrane phospholipid flip-flop during apoptosis. J Biol Chem. 1999;274:28113
  33. Kagan VE, Fabisiak JP, Shvedova AA, et al.  Oxidative signaling pathway for externalization of plasma membrane phosphatidylserine during apoptosis. FEBS Lett. 2002;477:1
  34. van Engeland M, Nieland LJ, Ramaekers FC, Schutte B, Reutelingsperger CP. Annexin V-affinity assay (A review on an apoptosis detection system based on phosphatidylserine exposure). Cytometry. 1998;31:1
  35. Zhivotovsky B, Samali A, Gahm A, Orrenius S. Caspases (Their intracellular localization and translocation during apoptosis). Cell Death Differ. 1999;6:644
  36. Mancini M, Nicholson DW, Roy S, et al.  The caspase-3 precursor has a cytosolic and mitochondrial distribution (implications for apoptotic signaling). J Cell Biol. 1998;140:1485
  37. Telford WG, Komoriya A, Packard BZ. Detection of localized caspase in early apoptotic cells by laser scanning cytometry. Cytometry. 2002;47:81
  38. Schimmer AD, Hedley DW, Penn LZ, Minden MD. Receptor- and mitochondrial-mediated apoptosis in acute leukemia (A translation view). Blood. 2001;98:3541

PII: S0301-472X(02)00894-9

Experimental Hematology
Volume 30, Issue 10 , Pages 1107-1114 , October 2002

Article Tools

* Image Usage & Resolution