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Cyclin-dependent kinase inhibitors block erythrocyte invasion and intraerythrocytic development of Babesia bovis in vitro

Published online by Cambridge University Press:  18 July 2007

K. NAKAMURA
Affiliation:
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan
N. YOKOYAMA
Affiliation:
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan
I. IGARASHI*
Affiliation:
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan
*
*Corresponding author. Tel: +81 155 49 5641. Fax: +81 155 49 5643. E-mail: [email protected]

Summary

Cyclin-dependent kinases (CDKs) are essential for the regulation of the eukaryotic cell cycle. A number of chemicals, which selectively inhibit the CDK activities, have been synthesized for the development of anti-cancer drugs. This report describes the inhibitory effect of purine derivatives known to be CDK inhibitors on the asexual growth of Babesia bovis. The 4 compounds, roscovitine, purvalanol A, CGP74514A, and CDK2 Inhibitor II, showed significantly suppressive effects on the in vitro growth of B. bovis. Three (roscovitine, purvalanol A, and CDK2 Inhibitor II) showed an inhibitory effect on the early stages of intraerythrocytic development of B. bovis. CGP74514A (CDK1-specific inhibitor) blocked the erythrocyte invasion by merozoites. Our data suggest the chemotherapeutic potential of the CDK inhibitors for babesiosis, and the target molecules of the compounds would participate in the process of successful erythrocyte invasion or intraerythrocytic development of B. bovis.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2007

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References

REFERENCES

Becker, F., Murthi, K., Smith, C., Come, J., Costa-Roldán, N., Kaufmann, C., Hanke, U., Degenhart, C., Baumann, S., Wallner, W., Huber, A., Dedier, S., Dill, S., Kinsman, D., Hediger, M., Bockovich, N., Meier-Ewert, S., Kluge, A. F. and Kley, N. (2004). A three-hybrid approach to scanning the proteome for targets of small molecule kinase inhibitors. Chemistry and Biology 11, 211223.CrossRefGoogle ScholarPubMed
Bock, R., Jackson, L., de Vos, A. and Jorgensen, W. (2004). Babesiosis of cattle. Parasitology 129 (Suppl.), S247S269.Google Scholar
Bork, S., Yokoyama, N., Matsuo, T., Clavelia, F. G., Fujisaki, K. and Igarashi, I. (2003). Clotrimazole, ketoconazole, and clodinafop-propargyl inhibit the in vitro growth of Babesia bigemina and Babesia bovis (Phylum Apicomplexa), Parasitology 127, 311315.CrossRefGoogle ScholarPubMed
Bork, S., Yokoyama, N., Ikehara, Y., Kumar, S., Sugimoto, C. and Igarashi, I. (2004). Growth-inhibitory effect of heparin on Babesia parasites. Antimicrobial Agents and Chemotherapy 48, 236241.Google Scholar
Bork, S., Okamura, M., Matsuo, T., Kumar, S., Yokoyama, N. and Igarashi, I. (2005). Host serum modifies the drug susceptibility of Babesia bovis in vitro. Parasitology 130, 489492.Google Scholar
Bork, S., Das, S., Okubo, K., Yokoyama, N. and Igarashi, I. (2006). Effects of protein kinase inhibitors on the in vitro growth of Babesia bovis. Parasitology 132, 775779.CrossRefGoogle ScholarPubMed
Chang, Y.-T., Gray, N. S., Rosania, G. R., Sutherlin, D. P., Kwon, S., Norman, T. C., Sarohia, R., Leost, M., Meijer, L. and Schultz, P. G. (1999). Synthesis and application of functionally diverse 2,6,9-trisubstituted purine libraries as CDK inhibitors. Chemistry and Biology 6, 361375.CrossRefGoogle Scholar
Dai, Y., Dent, P. and Grant, S. (2002). Induction of apoptosis in human leukemia cells by the CDK1 inhibitor CGP74514A. Cell Cycle 1, 143152.CrossRefGoogle ScholarPubMed
Davis, S. T., Benson, B. G., Bramson, H. N., Chapman, D. E., Dickerson, S. H., Dold, K. M., Eberwein, D. J., Edelstein, M., Frye, S. V., Gampe, R. T. Jr., Griffin, R. J., Harris, P. A., Hassell, A. M., Holmes, W. D., Hunter, R. N., Knick, V. B., Lackey, K., Lovejoy, B., Luzzio, M. J., Murray, D., Parker, P., Rocque, W. J., Shewchuk, L., Veal, J. M., Walker, D. H. and Kuyper, L. F. (2001). Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors. Science 291, 134137.CrossRefGoogle ScholarPubMed
De Vries, E., Corton, C., Harris, B., Cornelissen, A. W. C. A. and Berriman, M. (2006). Expressed sequence tag (EST) analysis of the erythrocytic stages of Babesia bovis. Veterinary Parasitology 138, 6174.Google Scholar
Franssen, F. F. J., Gaffar, F. R., Yatsuda, A. P. and de Vries, E. (2003). Characterisation of erythrocyte invasion by Babesia bovis merozoites efficiently released from their host cell after high-voltage pulsing. Microbes and Infection 5, 365372.CrossRefGoogle ScholarPubMed
Geyer, J. A., Prigge, S. T. and Waters, N. C. (2005). Targeting malaria with specific CDK inhibitors. Biochimica et Biophysica Acta 1754, 160170.CrossRefGoogle ScholarPubMed
Gray, N. S., Wodicka, L., Thunnissen, A.-M. W. H., Norman, T. C., Kwon, S., Espinoza, F. H., Morgan, D. O., Barnes, G., LeClerc, S., Meijer, L., Kim, S.-H., Lockhart, D. J. and Schultz, P. G. (1998). Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors. Science 281, 533538.CrossRefGoogle ScholarPubMed
Harmse, L., van Zyl, R., Gray, N., Schultz, P., Leclerc, S., Meijer, L., Doerig, C. and Havlik, I. (2001). Structure-activity relationships and inhibitory effects of various purine derivatives on the in vitro growth of Plasmodium falciparum. Biochemical Pharmacology 62, 341348.CrossRefGoogle ScholarPubMed
Knockaert, M., Gray, N., Damiens, E., Chang, Y.-T., Grellier, P., Grant, K., Fergusson, D., Mottram, J., Soete, M., Dubremetz, J.-F., Le Roch, K., Doerig, C., Schultz, P. G. and Meijer, L. (2000). Intracellular targets of cyclin-dependent kinase inhibitors: identification by affinity chromatography using immobilized inhibitors. Chemistry and Biology 7, 411422.Google Scholar
Knockaert, M., Greengard, P. and Meijer, L. (2002). Pharmacological inhibitors of cyclin-dependent kinases. Trends in Pharmacological Science 23, 417425.Google Scholar
Kuttler, K. L. (1988). World-wide impact of babesiosis. In Babesiosis of Domestic Animals and Man (ed. Ristic, M.), pp. 122. CRC Press, Inc., Boca Raton, Florida.Google Scholar
Meijer, L., Borgne, A., Mulner, O., Chong, J. P. J., Blow, J. J., Inagaki, N., Inagaki, M., Delcros, J.-G. and Moulinoux, J.-P. (1997). Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. European Journal of Biochemistry 243, 527536.CrossRefGoogle ScholarPubMed
Morgan, D. O. 1995. Principles of CDK regulation. Nature, London 374, 131134.CrossRefGoogle ScholarPubMed
Okubo, K., Yokoyama, N., Takabatake, N., Okamura, M. and Igarashi, I. (2006). Amount of cholesterol in host membrane affects erythrocyte invasion and replication by Babesia bovis. Parasitology 134, 625630.CrossRefGoogle ScholarPubMed
Senderowicz, A. M. and Sausville, E. A. (2000). Preclinical and clinical development of cyclin-dependent kinase modulators. Journal of the National Cancer Institute 92, 376387.Google Scholar
Vesely, J., Havlicek, L., Strnad, M., Blow, J. J., Donella-Deana, A., Pinna, L., Letham, D. S., Kato, J., Detivaud, L., LeClerc, S. and Meijer, L. (1994). Inhibition of cyclin-dependent kinases by purine analogues. European Journal of Biochemistry 224, 771786.Google Scholar
Vial, H. J. and Gorenflot, A. (2006). Chemotherapy against babesiosis. Veterinary Parasitology 138, 147160.Google Scholar
Ward, G. E., Fujioka, H., Aikawa, M. and Miller, L. H. (1994). Staurosporine inhibits invasion of erythrocytes by malarial merozoites. Experimental Parasitology 79, 480487.CrossRefGoogle ScholarPubMed
Wright, I. G. and Goodger, B. V. (1988) Pathogenesis of babesiosis. In Babesiosis of Domestic Animals and Man (ed. Ristic, M.), pp. 99118. CRC Press, Inc., Boca Raton, Florida.Google Scholar