Skip to content
BY-NC-ND 3.0 license Open Access Published by De Gruyter April 9, 2008

The induction of apoptosis by daunorubicin and idarubicin in human trisomic and diabetic fibroblasts

  • Sylwia Dragojew EMAIL logo , Agnieszka Marczak , Janusz Maszewski , Krzysztof Ilnicki and Zofia Jóźwiak

Abstract

In this study, we investigated apoptosis induced in human trisomic and diabetic fibroblasts by daunorubicin (DNR) and its derivative, idarubicin (IDA). The cells were incubated with DNR or IDA for 2 h and then cultured in a drug-free medium for a further 2–48 h. The apoptosis in the cultured cell lines was assessed by biochemical analysis. We found that both drugs induced a timedependent loss of mitochondrial membrane potential, and a significant increase in intracellular calcium and caspase-3 activity. Mitochondrial polarization and changes in the level of intracellular calcium were observed during the first 2–6 h after drug treatment. Caspase-3 activation occurred in the late stages of the apoptotic pathway. Our findings also demonstrated that idarubicin was more cytotoxic and more effective than daunorubicin in inducing apoptosis in trisomic and diabetic fibroblasts.

[1] Goebel, M. Oral idarubicin-an anthracycline derivative with unique properties. Ann. Hematol. 66 (1993) 33–43. http://dx.doi.org/10.1007/BF0173768710.1007/BF01737687Search in Google Scholar

[2] Berman, E. and McBride, M. Comparative cellular pharmacology of daunorubicin and idarubicin in human multidrug-resistant leukemia cells. Blood 79 (1992) 3267–3273. Search in Google Scholar

[3] Mazue, G., Iatropoulos, M., Imondi, A., Castellino, S., Brughera, M., Podesta, A., Della Torre, P. and Moneta, D. Anthracyclines: A review of general and special toxicity studies. Int. J. Oncol. 7 (1995) 713–726. Search in Google Scholar

[4] Quillet-Mary, A., Mansat, V., Duchayne, E., Come, M.G., Allouche, M., Bailly, J.D., Bordier, C. and Laurent, G. Daunorubicin-induced internucleosomal DNA fragmentation in acute myeloid cell lines. Leukemia 10 (1996) 417–425. Search in Google Scholar

[5] Masquelier, M., Zhou, Q.F., Gruber, A. and Vitols, S. Relationship between daunorubicin concentration and apoptosis induction in leukemic cells. Biochem. Pharmacol. 67 (2004) 1047–1058. http://dx.doi.org/10.1016/j.bcp.2003.10.02510.1016/j.bcp.2003.10.025Search in Google Scholar

[6] Chen, J-S., Chai, M-Q., Chen, H., Zhao, S. and Song, J. Regulation of phospholipase D activity and ceramide production in daunorubicin-induced apoptosis in A-431 cells. Biochim. Biophys. Acta 1488 (2000) 219–232. Search in Google Scholar

[7] Gervasoni, J.E., Hindenburg, A., Vezeridis, M., Shulze, S., Wanebo, H.J. and Mehta, S. An effective in vitro antitumor response against human pancreatic carcinoma with paclitaxel and daunorubicin by induction of both necrosis and apoptosis. Anticancer Res. 24 (2004) 2617–2626. Search in Google Scholar

[8] Liu, F.T., Kelsey, S.M., Newland, A.C. and Jia, L. Generation of reactive oxygen species is not involved in idarubicin-induced apoptosis in human leukaemic cells. Br. J. Haematol. 115 (2001) 817–825. http://dx.doi.org/10.1046/j.1365-2141.2001.03216.x10.1046/j.1365-2141.2001.03216.xSearch in Google Scholar

[9] Willmore, E., Errington, F., Tilby, M.J. and Austin, C.A. Formation and longevity of idarubicin-induced DNA topoisomerase II cleavable complexes in K562 human leukaemia cells. Biochem. Pharmacol. 63 (2002) 1807–1815. http://dx.doi.org/10.1016/S0006-2952(02)00920-610.1016/S0006-2952(02)00920-6Search in Google Scholar

[10] Pytel, D., Wysocki, T. and Majsterek, J. Comparative study of DNA damage, cell cycle and apoptosis in human K562 and CCRF-CEM leukemia cells: Role of BCR/ABL in therapeutic resistance. Comp. Biochem. Physiol. Part C 144 (2006) 85–92. Search in Google Scholar

[11] Vermeulen, K., van Bockstaele, D.K. and Berneman, Z.N. Apoptosis: mechanisms and relevance in cancer. Ann. Hematol. 84 (2005) 627–639. http://dx.doi.org/10.1007/s00277-005-1065-x10.1007/s00277-005-1065-xSearch in Google Scholar

[12] Jabs, T. Reactive oxygen intermediates as mediators of programmed cell death in plants and animals. Biochem. Pharmacol. 57 (1999) 231–245. http://dx.doi.org/10.1016/S0006-2952(98)00227-510.1016/S0006-2952(98)00227-5Search in Google Scholar

[13] Robertson, P.P. and Harmon, J.S. Diabetes, glucose toxicity, and oxidative stress: A case of double jeopardy for the pancreatic islet β cell. Free Radic. Biol. Med. 41 (2006) 177–184. http://dx.doi.org/10.1016/j.freeradbiomed.2005.04.03010.1016/j.freeradbiomed.2005.04.030Search in Google Scholar

[14] Zatorska, A., Maszewski, J. and Jóźwiak, Z. Changes in GSH-antioxidant system induced by daunorubicin in human normal and diabetic fibroblasts. Acta Biochim. Pol. 50 (2003) 825–835. Search in Google Scholar

[15] Kiyomiya, K., Matsuo, S. and Kurebe, M. Proteasome is a carrier to translocate doxorubicin from cytoplasm into nucleus. Life Sci. 62 (1998) 1853–1860. http://dx.doi.org/10.1016/S0024-3205(98)00151-910.1016/S0024-3205(98)00151-9Search in Google Scholar

[16] Özgen, U., Savasan, S., Buck, S. and Ravindranath, Y. Comparison of DiOC6(3) uptake and annexin V labeling for quantification of apoptosis in leukemia cells and non-malignant T lymphocytes from children. Cytometry 42 (2000) 74–78. http://dx.doi.org/10.1002/(SICI)1097-0320(20000215)42:1<74::AID-CYTO11>3.0.CO;2-610.1002/(SICI)1097-0320(20000215)42:1<74::AID-CYTO11>3.0.CO;2-6Search in Google Scholar

[17] Mulvaney, J.M., Zhang, T., Fewtrell, C. and Roberson, M.S. Calcium influx through L-type channels is required for selective activation of extracellular signal-regulated kinase by gonadotropin-releasing hormone. J. Biol. Chem. 274 (1999) 29796–29804. http://dx.doi.org/10.1074/jbc.274.42.2979610.1074/jbc.274.42.29796Search in Google Scholar

[18] Kania, K., Dragojew, S. and Jóźwiak, Z. Morphological and biochemical changes in human fibroblast lines induced by anthracyclines during apoptosis. Cell. Mol. Biol. Lett. 8 (2003) 121–126. Search in Google Scholar

[19] Hasle, H. Pattern of malignant disorders in individuals with Down’s syndrome. Lancet Oncol. 2 (2001) 429–436. http://dx.doi.org/10.1016/S1470-2045(00)00435-610.1016/S1470-2045(00)00435-6Search in Google Scholar

[20] Przybylska, M., Koceva-Chyła, A., Rózga, B. and Jóźwiak, Z. Cytotoxicity of daunorubicin in trisomic (+21) human fibroblasts: Relation to drug uptake and cell membrane fluidity. Cell Biol. Int. 25 (2001) 157–170. http://dx.doi.org/10.1006/cbir.2000.058310.1006/cbir.2000.0583Search in Google Scholar

[21] Jędrzejczak, M., Koceva-Chyła, A., Gwoździński, K. and Jóźwiak, Z. Changes in plasma membrane fluidity of immortal rodent cells induced by anticancer drugs doxorubicin, aclarubicin and mitoxantrone. Cell Biol. Int. 23 (1999) 497–506. http://dx.doi.org/10.1006/cbir.1999.039910.1006/cbir.1999.0399Search in Google Scholar

[22] Huigsloot, M., Tijdens, I.B., Mulder, G.J. and van de Water, B. Differential regulation of doxorubicin-induced mitochondrial dysfunction and apoptosis by Bcl-2 in mammary adenocarcinoma (MTLn3) cells. J. Biol. Chem. 277 (2002) 35869–35879. http://dx.doi.org/10.1074/jbc.M20037820010.1074/jbc.M200378200Search in Google Scholar

[23] Hanada, M., Noguchi, T. and Yamaoka, T. Amrubicin induces apoptosis in human tumor cells mediated by the activation of caspase-3/7 preceding a loss of mitochondrial membrane potential. Cancer Sci. 97 (2006) 1396–1403. http://dx.doi.org/10.1111/j.1349-7006.2006.00318.x10.1111/j.1349-7006.2006.00318.xSearch in Google Scholar

[24] Ray, S.K., Fidan, M., Nowak, M.W., Wilford, G.G., Hogan, E.L. and Banik, N.L. Oxidative stress and Ca2+ influx upregulate calpain and induce apoptosis in PC 12 cells. Brain Res. 852 (2000) 326–334. http://dx.doi.org/10.1016/S0006-8993(99)02148-410.1016/S0006-8993(99)02148-4Search in Google Scholar

[25] McConkey, D.J. and Orrenius, S. The role of calcium in regulation of apoptosis. Biochem. Biophys. Res. Commun. 239 (1997) 357–366. http://dx.doi.org/10.1006/bbrc.1997.740910.1006/bbrc.1997.7409Search in Google Scholar PubMed

[26] Mathiasen, I.S., Sergeev, I.N., Bastholm, L., Elling, F., Norman, A.W. and Jaattela, M. Calcium and calpain as key mediators of apoptosis-like death induced by vitamin D compounds in breast cancer cells. J. Biol. Chem. 277 (2002) 30738–30745. http://dx.doi.org/10.1074/jbc.M20155820010.1074/jbc.M201558200Search in Google Scholar PubMed

[27] Turnbull, K.J., Brown, B.L. and Dobson, P.R. Caspase-3-like activity is necessary but not sufficient for daunorubicin induced apoptosis in Jurkat human lymphoblastic leukemia cells. Leukemia 13 (1999) 1056–1061. http://dx.doi.org/10.1038/sj/leu/240143810.1038/sj/leu/2401438Search in Google Scholar

[28] Bellarosa, D., Ciucci, A., Bullo, A., Nardelli, F., Manzini, S., Maggi, C.A. and Goso, C. Apoptotic events in a human ovarian cancer cell line exposed to anthracyclines. J. Pharmacol. Exp. Ther. 296 (2001) 276–283. Search in Google Scholar

[29] Dartsch, D.C., Schaefer, A., Boldt, S., Kolch, W. and Marquardt, H. Comparison of anthracycline-induced death of human leukemia cells: Programmed cell death versus necrosis. Apoptosis 7 (2002) 537–548. http://dx.doi.org/10.1023/A:102064721155710.1023/A:1020647211557Search in Google Scholar

[30] Anneren, G. and Epstein, C.J. Lipid peroxidation and superoxide dismutase-1 and glutathione peroxidase activities in trisomy 16 fetal mice and human trisomy 21 fibroblasts. Pediatr. Res. 21 (1987) 88–92. http://dx.doi.org/10.1203/00006450-198701000-0001910.1203/00006450-198701000-00019Search in Google Scholar

[31] Zatorska, A. and Jóźwiak, Z. Involvement of glutathione and glutathione related enzymes in the protection of normal and trisomic human fibroblasts against daunorubicin Cell. Biol. Int. 26 (2002) 383–391. http://dx.doi.org/10.1006/cbir.2002.086110.1006/cbir.2002.0861Search in Google Scholar

[32] Pelsman, A., Hoyo-Vadillo, C., Gudasheva, T.A., Seredenin, S.B., Ostrovskaya, R.U. and Busciglio, J. GVS-111 prevents oxidative damage and apoptosis in normal and Down’s syndrome human cortical neurons. Int. J. Dev. Neurosci. 21 (2003) 117–124. http://dx.doi.org/10.1016/S0736-5748(03)00031-510.1016/S0736-5748(03)00031-5Search in Google Scholar

[33] Anderson, A.J., Stoltzner, S., Lai, F., Su, J. and Nixon, R.A. Morphological and biochemical assessment of DNA damage and apoptosis in Down syndrome and Alzheimer disease, and effect of postmortem tissue archival on TUNEL. Neurobiol. Aging 21 (2000) 511–524. http://dx.doi.org/10.1016/S0197-4580(00)00126-310.1016/S0197-4580(00)00126-3Search in Google Scholar

[34] Busciglio, J. and Yanker, B.A. Apotosis and increased generation of reactive oxygen species in Down’s syndrome neurons in vitro. Nature 378 (1995) 776–779. http://dx.doi.org/10.1038/378776a010.1038/378776a0Search in Google Scholar PubMed

[35] Paz-Miguel, J.E., Flores, R., Sanchez-Velasco, P., Ocejo-Vinyals, G., de Diego, J.E., de Rego, J. and Leyva-Cobian, F. Reactive oxygen intermediates during programmed cell death induced in the thymus of the Ts(1716)65Dn mouse, a murine model for human Down’s syndrome. J. Immunol. 163 (1999) 5399–5410. Search in Google Scholar

[36] Gulesserian, T., Engidawork, E., Yoo, B.C., Cairns, N. and Lubec, G. Alteration of caspases and other apoptosis regulatory proteins in Down syndrome. J. Neural. Transm. 61 (2001) 163–179. Search in Google Scholar

[37] Mohr, S., Xi, X., Tang, J. and Kern, T.S. Caspase activation in retinas of diabetic and galactosemic mice and diabetic patients. Diabetes 51 (2002) 1172–1179. http://dx.doi.org/10.2337/diabetes.51.4.117210.2337/diabetes.51.4.1172Search in Google Scholar PubMed

[38] Cai, L., Li, W., Wang, G.W., Guo, L.P., Jiang, Y.C. and Kang, Y.J. Hyperglycemia-induced apoptosis in mouse myocardium-mitochondrial cytochrome c — mediated caspase-3 activation pathway. Diabetes 51 (2002) 1938–1948. http://dx.doi.org/10.2337/diabetes.51.6.193810.2337/diabetes.51.6.1938Search in Google Scholar PubMed

[39] Schmeichel, A.M., Schmelzer, J.D. and Low, P.A. Oxidative injury and apoptosis of dorsal root ganglion neurons in chronic experimental diabetic neuropathy. Diabetes 52 (2003) 165–171. http://dx.doi.org/10.2337/diabetes.52.1.16510.2337/diabetes.52.1.165Search in Google Scholar PubMed

[40] Roat, E., Prada, N., Ferraresi, R., Giovenzana, Ch., Nasi, M., Troiano, L., Pinti, M., Nemes, E., Lugli, E., Biagioni, O., Mariotti, M., Ciacci, L., Consolo, U., Balli, F and Cossarizza, A. Mitochondrial alterations and tendency to apoptosis in peripheral blood cells from children with Down syndrome. FEBS Lett. 581 (2007) 521–525. http://dx.doi.org/10.1016/j.febslet.2006.12.05810.1016/j.febslet.2006.12.058Search in Google Scholar PubMed

Published Online: 2008-4-9
Published in Print: 2008-6-1

© 2007 University of Wrocław, Poland

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Downloaded on 22.5.2024 from https://www.degruyter.com/document/doi/10.2478/s11658-007-0045-7/html
Scroll to top button