The Effect of Hemin and Deferoxamine on Selenium, Zinc, and Iron Levels of K562 Cells
Bahire Küçükkaya, Lale Afrasyap
DOI: 10.4236/jct.2011.21007   PDF    HTML     4,240 Downloads   9,208 Views   Citations


This study investigated contents of trace elements selenium, zinc and iron both in control K562 cells, human leukemia cell line, and cells treated with hemin or the iron chelator deferoxamine cells. K562 cell line was grown in RPMI medium supplemented with 10% fetal calf serum, 100 IU/mL penicillin, 100 μg/mL streptomycin, 25 μg/mL amphotericin B and 2 mM L-glutamine at 37?C in humidified air containing 5% CO2. K562 cells were treated with hemin and deferoxamine from the first day to the fifth day. The trace element levels were measured by inductively coupled plasma optical emission spectrometry. Treatment of K562 cells with hemin resulted in an increase in the levels of selenium on fifth day compared with first day. No differences were observed in selenium levels of the control group compared with the hemin-induced group. Also there were no significant differences observed in the zinc levels of control cells compared with deferoxamine- and hemin-induced cells. Iron levels of hemin-induced cells were decreased on the fourth day com-pared with the third day. On the third day, iron levels of hemin-induced cells were significantly increased compared to the control group. Our observations suggest that alterations of selenium and zinc levels may play a role in hemin-induction and deferoxamine-inhibition, respectively. On the other hand, iron levels may influence both in hemin-induction and deferoxamine-inhibition of K562 human leukemia cell line

Share and Cite:

B. Küçükkaya and L. Afrasyap, "The Effect of Hemin and Deferoxamine on Selenium, Zinc, and Iron Levels of K562 Cells," Journal of Cancer Therapy, Vol. 2 No. 1, 2011, pp. 65-70. doi: 10.4236/jct.2011.21007.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] C. G. Fraga, “Relevance, Essentiality and Toxicity of Trace Elements in Human Health,” Molecular Aspects of Medicine, Vol. 26, No. 4-5, August 2005, pp. 235-244. doi:10.1016/j.mam.2005.07.013
[2] M. Allg?wer, G. A. Schoenenberger and B. G. Sparkes, “Burning the Largest Immune Organ,” Burns, Vol. 21, Suppl. 1, 1995, pp. S7-47. doi:10.1016/0305-4179(95)90028-4
[3] H. H. Sandstead, “Understanding Zinc: Recent Observation and Interpretations,” Journal of Laboratory and Clinical Medicine, Vol. 124, No. 3, September 1994, pp. 322-327.
[4] M. M. Berger, F. Spertini, A. Shenkin, C. Wardle, L. Wiesner, C. Schindler and R. L. Chiolero, “Trace Element Supplementation Modulates Pulmonary Infection Rates after Major Burns: A Double-Blind, Placebo-Controlled Trial,” The American Journal of Clinical Nutrition, Vol. 68, No. 2, August 1998, pp. 365-371.
[5] K. S. Abul-Hassan, B. E. Lehnert, L. Guant and R. Walmsley, “Abnormal DNA Repair in Selenium-Treated Human Cells,” Mutation Research, Vol. 565, No. 1, December 2004, pp. 45-51.
[6] C. B. Allan, G. M. Lacourciere and T. C. Stadtman, “Responsiveness of Selenoproteins to Dietary Selenium,” Annual Review of Nutrition, Vol. 19, 1999, pp. 1-16. doi:10.1146/annurev.nutr.19.1.1
[7] H. Zeng and G. F. Combs, “Selenium as an Anticancer Nutrient: Roles in Cell Proliferation and Tumor Cell Invasion,” The Journal of Nutritional Biochemistry, Vol. 19, No. 1, January 2008, pp. 1-7. doi:10.1016/j.jnutbio.2007.02.005
[8] C. Ip, H. J. Thompson and H. E. Ganther, “Selenium Modulation of Cell Proliferation and Cell Cycle Biomarkers in Normal and Premalignant Cells of the Rat Mammary Gland,” Cancer Epidemiology, Biomarkers Prevention, Vol. 9, No. 1, January 2000, pp. 49-54.
[9] B. L. Vallee and K. H. Falchuk, “The Biochemical Basis of Zinc Physiology,” Physiological Reviews, Vol. 73, No. 1, January 1993, pp. 79-118.
[10] D. Beyersmann and H. Haase, “Functions of Zinc in Signaling, Proliferation and Differentiation of Mammalian Cells,” Biometals, Vol. 14. No. 3-4, September 2001, pp. 331-341. doi:10.1023/A:1012905406548
[11] L. Brard, C. O. Granai and N. Swamy, “Iron Chelators Deferoxamine and Diethylenetriamine Pentaacetic Acid Induce Apoptosis in Ovarian Carcinoma,” Gynecologic Oncology, Vol. 100, No. 1, January 2006, pp. 116-127. doi:10.1016/j.ygyno.2005.07.129
[12] C. B. Lozzio and B. B. Lozzio, “Human Chronic Myelogenous Leukemia Cell Line with Positive Philadelphia Chromosome,” Blood, Vol. 45, March 1975, pp. 321-334.
[13] T. R. Rutherford, J. B. Clegg and D. J. Weatherall, “K562 Human Leukemia Cells Synthetize Embryonic Hemoglobin in Response to Hemin,” Nature, Vol. 280, No. 5718, July 1979, pp. 164-165. doi:10.1038/280164a0
[14] P. Charnay and T. Maniatis, “Transcriptional Regulation of Globin Gene Expression in the Human Erythroid Cell Line K562,” Science, Vol. 220, January 1983, pp. 1281-1283. doi:10.1126/science.6574602
[15] S. Sassa and T. Nagai, “The Role of Heme in Gene Expression,” International Journal of Hematology, Vol. 63, No. 3, April 1996, pp. 167-178. doi:10.1016/0925-5710(96)00449-5
[16] Y. Fukuda, H. Fujita, S. Taketani and S. Sassa, “Dimethyl Sulphoxide and Haemin Induce Ferrochelatase mRNA by Different Mechanisms in Murine Erythroleukaemia Cells,” British Journal of Haematology, Vol. 83, No. 3, March 1993, pp. 670-675. doi:10.1111/j.1365-2141.1993.tb03207.x
[17] A. Battistini, G. Marziali, R. Albertini, D. Bulgarini, E. M. Coccia, G. Fiorucci, G. Romeo, R. Orsatti, R. Testa, G. B. Rossi and C. Peschle, “Positive Modulation of Hemoglobin, Heme, and Transferring Receptor Synthesis by Murine Interferonalpha and Differentiating Friend Cells. Pivotal Role of Heme Synthesis,” Journal of Biological Chemistry, Vol. 266, No. 1, January 1991, pp. 528-535.
[18] E. M. Coccia, V. Profita, G. Fiorucci, G. Romeo, E. Affabris, U. Testa, M. W. Hentze and A. Battistini, “Modulation of Ferritin H-Chain Expression in Friend Erythroleukemia Cells: Transcriptional and Translational Regulation by Hemin,” Molecular and Cellular Biology, Cell Biology, Vol. 12, No. 7, July 2004, pp. 3015-3022.
[19] T. Tahara, J. Sun, K. Nakanishi, M. Yamamoto, H. Mori, T. Saito, H. Fujita, K. Igarashi and S. Taketan, “Heme Positively Regulates the Expression of Beta-Globin at the Locus Control Region via the Transcriptional Factor Bach1 in Erythroid Cells,” Journal of Biological Chemistry, Vol. 279, No. 7, February 2004, pp. 5480-5487.
[20] R. U. Haq, J. P. Werely and C. R. Chitambar, “Induction of Apoptosis by Iron Deprivation in Human Leukemic CCRF-CEM Cells,” Experimental Hematology, Vol. 23, No. 5, May 1995, pp. 428-432.
[21] D. L. Becton and P. Bryles, “Deferoxamine Inhibition of Human Neuroblastoma Viability and Proliferation,” Cancer Research, Vol. 48, No. 24, December 1988, pp. 7189-7192.
[22] C. Brodie, G. Siriwardana, J. Lucas, R. Schleicher, N. Terada, A. Szepesi, E. Gelfand and P. Seligman, “Neuroblastoma Sensitivity to Growth Inhibition by Desferrioxamine. Evidence for Block in G1 Phase of the Cell Cycle,” Cancer Research, Vol. 53, No. 17, September 1993, pp. 3968-3975.
[23] D. Richardson, P. Ponka and E. Baker, “The Effect of the Iron(III) Chelator, Desferrioxamine, on Iron and Transferring Uptake by the Human Malignant Melanoma Cell,” Cancer Research, Vol. 54, No. 3, February 1994, pp. 685- 689.
[24] H. W. Hann, M. W. Stahlhut and C. L. Hann, “Effect of Iron and Desferoxamine on Cell Growth and in vitro Ferritin Synthesis in Human Hepatoma Cell Lines,” Hepatology, Vol. 11, No. 4, April 1990, pp. 566-569. doi:10.1002/hep.1840110407
[25] T. Simonart, C. Degraef, G. Andrei, R. Mosselmans, P. Hermans, J. P. Van Vooren, J. C. Noel, J. R. Boelaert, R. Snoeck and M. Heenen, “Iron Chelators Inhibit the Grow- th and Induce the Apoptosis of Kaposi’s Sarcoma Cells and of Their Putative Endothelial Precursors,” Journal of Investigative Dermatology, Vol. 115, No. 5, November 2000, pp. 893-900. doi:10.1046/j.1523-1747.2000.00119.x
[26] T. Simonart, J. R. Boelaert, R. Mosselmans, G. Andre, J. C. Noel, E. De Clercq and R. Snoeck, “Antiproliferative and Apoptotic Effects of Iron Chelators on Human Cercival Carcinoma Cells,” Gynecologic Oncology, Vol. 85, No. 1, April 2002, pp. 95-102. doi:10.1006/gyno.2001.6570
[27] H. J. Lee, J. Lee, S. K. Lee and E. C. Kim, “Differential Regulation of Iron Chelator-Induced IL-8 Synthesis via MAP Kinase and NF-κB in Immortalized and Malignant Oral Keratinocytes,” BMC Cancer, Vol. 13, No. 7, September 2007, p. 176.
[28] M. A. Philippe, R. G. Ruddell and G. A. Ramm, “Role of Iron in Hepatic Fibrosis: Piece in the Puzzle,” World Journal of Gastroenterology, Vol. 13, No. 35, September 2007, pp. 4746-4754.
[29] D. Kyriakou, A. G. Eliopoulos, A. Papadakis, M. Alexandrakis and G. D. Eliopoulos, “Decreased Expression of C-myc Oncoprotein by Peripheral Blood Mononuclear Cells in Thalassaemia Patients Receiving Desferrioxamine,” European Journal of Haematology, Vol. 60, No. 1, January 1998, pp. 21-27.
[30] L. Cianetti, P. Segnalini, A. Calzolari, O. Morsilli, F. Felicetti, C. Ramoni, M. Gabbianelli, U. Testa and N. M. Sposi, “Expression of Alternative Transcripts of Ferroporin-1 during Human Erythroid Differentiation,” Haematologica, Vol. 90, No. 12, December 2005, pp. 1595- 1606.
[31] C. Callens, S. Coulon, J. Naudin, I. Radford-Weiss, E. Raffoux, P. H. Wang, S. Agarwal, H. Tamouza, E. Paubelle, V. Asnafi, J. A. Ribeil, P. Dessen, D. Canioni, O. Chandesris, M. T. Rubio, C. Beaumont, M. Benhamou, H. Dombret, E. Macintyre, R. C. Monteiro, I. C. Moura and O. Hermine, “Targeting Iron Homeostasis Induces Cellular Differentiation and Synergizes with Differentiating Agents in Acute Myeloid Leukemia,” The Journal of Experimental Medicine, Vol. 207, No. 4, April 2010, pp. 731-750. doi:10.1084/j
[32] I. U. Pardoe, K. K. Grewal, M. P. Baldeh, J. Hamid and A. T. Burness, “Persistent Infection of K562 Cells by Encephalomyocarditis Virus,” The Journal of Virology, Vol. 64, No. 12, December 1990, pp. 6040-6044.
[33] O. Kahklon, Y. Gruenbaum and Z. I. Cabantchik, “Repression of Ferritin Expression Increases the Labile Iron Pool, Oxidative Stress, and Short-Term Growth of Human Erythroleukemia Cells,” Blood, Vol. 97, No. 9, May 2001, pp. 2863-2871. doi:10.1182/blood.V97.9.2863
[34] X. F. Huo, J. Yu, H. Peng, Z. W. Du, X. L. Liu, Y. N. Ma, X. Zhang, Y. Zhang , H. L. Zhao and J. W. Zhang, “Differential Expression Changes in K562 Cells during the Hemin-Induced Erythroid Differentiation and the Phorbol Myristate Acetate (PMA)-Induced Megakaryocytic Differentiation,” Molecular and Cellular Biochemistry, Vol. 292, No. 1-2, November 2006, pp. 55-167.
[35] K. Iwasaki, E. L. Mackenzie, K. Hailemariam, K. Sakamoto and Y. Tsuji, “Hemin-Mediated Regulation of an Antioxidant-Responsive Element of the Human Ferritin H Gene and Role of Ref-1 during Rrythroid Differentiation of K562 Cells,” Molecular and Cellular Biology, Vol. 26, No. 7, April 2006, pp. 2845-2856. doi:10.1128/MCB.26.7.2845-2856.2006
[36] B. Kü?ükkaya, G. ?ztürk and L. Yal??ntepe, “Nitric Oxide Levels during Erythroid Differentiation in K562 Cell Line,” Indian Journal of Biochemistry and Biophysics, Vol. 43, No. 4, August 2006, pp. 251-253.
[37] B. Kucukkaya, D. O. Arslan and B. Kan, “Role of G Proteins and ERK Activation in Hemin-Induced Erythroid Differentiation of K562 Cells,” Life Sciences, Vol. 78, No. 11, February 2006, pp. 1217-1224. doi:10.1016/j.lfs.2005.06.041
[38] Y. Saito, Y. Yoshido, T. Akazawa, K. Takahashi and E. Niki, “Cell Death Caused by Selenium Deficiency and Protective Effect of Antioxidants,” Journal of Biological Chemistry, Vol. 278, No. 41, October 2003, pp. 39428- 39434. doi:10.1074/jbc.M305542200
[39] K. H. Maclean, J. L. Cleveland and J. B. Porter, “Cellular Zinc Content is a Major Determinant of Iron Chelator-Induced Apoptosis of Thymocytes,” Blood, Vol. 98, No. 13, December 2001, pp. 3831-3839.
[40] W. Watjen, H. Haase, M. Biagioli and D. Beyersmann, “Induction of Apoptosis in Mammalian Cells by Cadmium and Zinc,” Environmental Health Perspectives, Vol. 5, suppl. 5, October 2002, pp. 865-867.
[41] O. Alcantara and D. H. Boldt, “Iron Deprivation Blocks Multilineage Haematopoietic Differentiation by Inhibiting Induction of p21 (WAF1/CIP1),” British Journal of Haematology, Vol. 137, No. 3, May 2007, pp. 252-261. doi:10.1111/j.1365-2141.2007.06549.x

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.