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The intrinsic or the extrinsic pathways of apoptosis in the epidermis after cladribine application?

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DOI: 10.4236/jbise.2013.63033    2,811 Downloads   4,465 Views   Citations

ABSTRACT

Purpose: This study was aimed to assess the expression of caspase 8 and caspase 9 in the epidermis, during apoptosis after cladribine administration. Materials and Methods: The experiment was carried on 10 Wistar rats. The animals were placed into 2 groups: control group and experimental group. Animals in the control group, in addition to standard feed and water, were injected with a physiological salt in a quantity corresponding to the drug dosage, over the course of the experiment. The experimental group animals were treated with cladribine in the dose of 0.07 mg/kg/24h, for 6 consecutive days in the morning, in 3 cycles with a 5-week gap in administering the drug. After the completion of the experiment, the animals were decapitated, and full thickness slices of skin were taken from all the rats for immunohisto- chemical study. The results of the statistical surveys were analysed in Statistica 10.0. The difference in intensity of expression of caspase 9 and caspase 8 in the groups were investigated using the Chiquadrat test. Statistical significance was considered at p < 0.05. Results: The statistical analysis found significant correlation in expression of caspase 9 between examined groups (p < 0.0001). There were no statistical relationships in the presence of the expression of caspase 8 between examined groups (p = 0.0526). Conclusion: Our findings suggest that mechanism of apoptosis in the rats’ epidermis, induced by cladribine given in the scheme used in the treatment of MS in humans, involves caspase 9 activity. This means that 2-CdA initiates the intrinsic apoptosis pathway.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Chylinska-Wrzos, P. , Wawryk-Gawda, E. , Lis-Sochocka, M. , Jedrych, M. , Lancut, M. , Bulak, K. , Leszcz-Stankiewicz, J. and Jodlowska-Jedrych, B. (2013) The intrinsic or the extrinsic pathways of apoptosis in the epidermis after cladribine application?. Journal of Biomedical Science and Engineering, 6, 265-272. doi: 10.4236/jbise.2013.63033.

References

[1] Robak, T., Lech-Maranda, E., Korycka, A. and Robak, E. (2006) Purine nucleoside analogs as immunosuppressive and antineoplastic agents: Mechanism of action and clinical activity. Current Medicinal Chemistry, 13, 3165-3189. doi:10.2174/092986706778742918
[2] Robak, T., Korycka, A., Lech-Maranda, E. and Robak, P. (2009) Current status of older and new purine nucleoside analogues in the treatment of lymphoproliferative diseases. Molecules, 14, 1183-1226. doi:10.3390/molecules14031183
[3] Leist, T.P. and Ver-mersch, P. (2007) The potential role for cladribine in the treat-ment of multiple sclerosis: Clinical experience and development of an oral tablet formulation. Current Medical Research & Opinion, 23, 2667- 2676. doi:10.1185/030079907X233142
[4] Leist, T.P. and Weissert, R. (2011) Cladribine: Mode of action and implications for treatment of multiple sclerosis. Clinical Neuropharmacology, 34, 28-35. doi: 10.1097/WNF.0b013e318204cd90
[5] Spurgeon, S., Yu, M., Phillips, J.D. and Epner, E.M. (2009) Cladribine: Not just another purine analogue? Expert Opinion on Investigational Drugs, 18, 1169-1181. doi:10.1517/13543780903071038
[6] Saven, A. and Piro, L.D. (1994) 2-Chlorodeoxyadenosine: A newer purine analog active in the treatment of indolent lymphoid malignancies. Annals of Internal Medicine, 120, 784-791.
[7] http://www.abcleki.pl/leki/biodribin
[8] Hartung, H.-P., Aktas,O., Kieseier, B. and Comi, G. (2010) Development of oral cladribine for the treatment of multiple sclerosis. Journal of Neurology, 257, 163-170. doi:10.1007/s00415-009-5359-0
[9] Maciejek, Z. (2005) Diagnostyka stwardnienia rozsianego. Farmakoterapia w Psy-chiatrii i Neurologii, 3, 209-217.
[10] Gasperini, C., Ruggieri, S. and Pozzilli, C. (2010) Emerg- ing oral treatments in multiple sclerosis-clinical utility of cladribine tablets. Therapeutics and Clinical Risk Management, 6, 391-399.
[11] Kasper, L.H. and Shoemaker, J. (2010) Multiple sclerosis immunology. The healthy immune system vs the MS immune system. Neurology, 74, S2-S8. doi:10.1212/WNL.0b013e3181c97c8f
[12] Losy, J. (2004) Patogeneza oraz aktualne kryteria diag- nostyczne stwardnienia rozsianego. Neurologia i Psychi- atria, 4, 53-56.
[13] Crews, K.R., Wimmer, P.S., Hudson, J.Q., Howard, S.C., Ribeiro, R.C. and Razzouk, B.I. (2002) Pharmacokinetics of 2-chlorodeoxyadenosine in a child undergoing hemo- filtration and hemodialysis for acute renal failure. Journal of Pediatric Hematology/Oncology, 24, 677-680. doi:10.1097/00043426-200211000-00016
[14] Ewald, B., Sampath, D. and Plunkett, W. (2008) Nucleo- side analogs: Molecular mechanisms signaling cell death. Oncogene, 27, 6522-6537. doi:10.1038/onc.2008.316
[15] Johnston, J.B. (2011) Mechanism of action of pentostatin and cladribine in hairy cell leukemia. Leuk Lymphoma, 52, 43-45. doi:10.3109/10428194.2011.570394
[16] Stańczyk, M. and Majsterek, I. (2008) Apoptoza-cel ukie-runkowanej terapii przeciwnowotworowej. Post?py Biologii Komórki, 35, 467-484.
[17] St?pień, A., Izdebska, M. and Grzanka, A. (2007) Rod- zaje ?mierci komórki. Post?py Higieny i Medycyny Do- ?wiadczalnej, 61, 420-428. http://www.phmd.pl/fulltxthtml.php?ICID=490830
[18] Badowska-Kozakiewicz, A.M. and Malicka, E. (2009) Apoptoza w nowotworach gruczo?u sutkowego u psów. ?ycie Weterynaryjne, 84, 902-905.
[19] Bielak-?mijewska, A. (2003) Mechanizmy odporno?ci komórek nowotworowych na apoptoz?. Kosmos Prob- lemy Nauk Biologicznych, 52, 157-171.
[20] Helewski, K.J., Kowalczyk-Ziomek, G.I. and Konecki, J. (2006) Apoptoza i martwica-dwie drogi do jednego celu. Wiadomo?ci Lekarskie, 59, 679-684.
[21] Hordyjewska, A. and Pasternak, K. (2005) Apoptotyczna ?mier? komórki. Advances in Clinical and Experimental Medicine, 14, 545-554. http://www.dbc.wroc.pl/Content/2100/a05-3-19_Hord.pdf
[22] Ola, M.S., Nawaz, M. and Ahsan, H. (2011) Role of Bcl- 2 family proteins and caspases in the regulation of apop- tosis. Molecular and Cellular Biochemistry, 351, 41-58. doi:10.1007/s11010-010-0709-x
[23] Rupinder, S.K., Gurpreet, A.K. and Manjeet, S. (2007) Cell suicide and caspases. Vascular Pharmacology, 46, 383-393. doi:10.1016/j.vph.2007.01.006
[24] Sampath, D., Rao, V.A. and Plunkett, W. (2003) Mecha- nism of apoptosis induction by nucleoside analogs. Oncogene, 22, 9063-9074. doi:10.1038/sj.onc.1207229
[25] Chowdhury, I., Tharakan, B. and Bhat, G.K. (2008) Caspases: An update. Comparative Biochemistry and Physiology B, 151, 10-27. doi:10.1016/j.cbpb.2008.05.010
[26] Inoue, S., Browne, G., Melino, G. and Cohen, G.M. (2009) Ordering of caspases in cells undergoing apoptosis by the intrinsic pathway. Cell Death & Differentiation, 16, 1053- 1061. doi:10.1038/cdd.2009.29
[27] Korzeniewska-Dyl, I. (2008) Kaspazy-nowy lek w terapii przeciwzapalnej i przeciwnowotworowej? Polski Merkuriusz Lekarski Medpress, 24, 5-7.
[28] Ritter, P.M., Marti, A., Blanc, C., Baltzer, A., Krajewski, S., Reed, J.C. and Jaggi, R. (2000) Nuclear localization of procaspase-9 and processing by a capsase-3-like activity in mammary epithelial cells. European Journal of Cell Biology, 79, 358-364. doi:10.1078/S0171-9335(04)70040-0
[29] Fan, T.-J., Han, L.-H., Cong, R.-S. and Liang, J. (2005) Caspase family pro-teases and apoptosis. Acta Biochimica et Biophysica Sinica, 37, 719-727. doi:10.1111/j.1745-7270.2005.00108.x
[30] Kl?pfer, A., Ha-senj?ger, A., Belka, C., Schulze-Osthoff, K., D?rken, B. and Daniel, P.T. (2004) Adenine deoxy-nucleotides fludarabine and cladribine induces apoptosis in a CD95/Fas receptor, FADD and caspase-8-independent manner by activation of the mitochondrial cell death pathway. Oncogene, 23, 9408-9418. doi:10.1038/sj.onc.1207975
[31] Marzo, I., Pérez-Galán, P., Giraldo, P., Rubio-Felix, D., Anel, A. and Naval, J. (2001) Cladribine induces apop- tosis in human leukaemia cells by caspase-dependent and -independent pathways acting on mito-chondria. Biochemistry Journal, 359, 537-546. doi:10.1042/0264-6021:3590537
[32] Nomura, Y., Inanami, O., Takahashi, K., Matsuda, A. and Kuwabara, M. (2000) 2-Chloro-2’-deoxyadenosine induces apoptosis through the Fas/Fas ligand pathway in human leukemia cell line MOLT-4. Leukemia, 14, 299-306. doi:10.1038/sj.leu.2401649
[33] Roterman-Konieczna, I. (2010) Statystyka na recept?. Wprowadzenie do statystyki medycznej. Wydawnictwo Uniwersytetu Jagiellońskiego, Warszawa.
[34] Conrad, D.M., Robichaud, M.R.J., Mader, J.S., Boudreau, R.T.M., Richardson, A.M., Giacomantonio, C.A. and Ho- skin. D/W. (2008) 2-Chloro-2’-deoxyadenosine-induced apoptosis in T leukemia cells is mediated via a caspase-3-dependent mitochondrial feedback amplification loop. International Journal of Oncology, 32, 1325-1333.
[35] Pérez-Galán, P., Marzo, I., Giraldo, P., Rubio-Félix, D., Lasierra, P., Larrad, L., Anel, A. and Naval, J. (2002) Role of caspases and apoptosis-inducing factor (AIF) in cladribine-induced apoptosis of B cell chronic lympho-cytic leukemia. Leukemia, 16, 2106-2114. doi:10.1038/sj.leu.2402650
[36] Ceruti, S., Beltrami, E., Matarrese, P., Mazzola, A., Cattabeni, F., Malorni, W. and Ab-bracchiao, M.P. (2003) A key role for caspase-2 and caspase-3 in the apoptosis induced by 2-chloro-2’-deoxy-adenisine (cla-dribine) and 2-chloro-adenosine in human astrocytoma cells. Molecular Pharmacology, 63, 1437-1447. doi:10.1124/mol.63.6.1437

  
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