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Vol. 52, No. 5, 2006
Issue release date: August 2006

Iron(III) Chloride Hexahydrate Does Not Enhance Methotrexate Cytotoxicity on Saccharomyces cerevisiae

Ruiz-Gómez M.J. · Martínez-Morillo M.
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Methotrexate is a potent inhibitor of dihydropholate reductase that has been used as effective antineoplastic treatment due to its capacity to inhibit cell growth. In a previous work published in Bioelectrochemistry 2003;60:81—86, we reported a statistically significant increment of 40.1 and 29.4% in methotrexate potency when MCF-7 breast cancer cells were exposed simultaneously to iron(III) chloride hexahydrate (FeCl3·6H2O) and methotrexate. The aim of this study was to investigate whether iron(III) could produce, on a Saccharomyces cerevisiae wild-type strain, alterations on methotrexate potency by the drop test survival assay and proliferation studies measured after 24 and 96 h of exposure. The data presented in the current report indicate that FeCl3·6H2O (1, 10, 100 and 500 µg/ml) does not induce modulation of the action of methotrexate (10, 100 and 500 µg/ml) in S. cerevisiae yeast cells when they are exposed simultaneously for 24 and 96 h.

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  1. Kang Y, Perry RR: Effect of a-interferon on P-glycoprotein expression and function and on verapamil modulation of doxorubicin resistance. Cancer Res 1994;54:2952–2958.
  2. Souviron Rodríguez A, Ruiz Gómez MJ, Morales Moreno JA, Martínez Morillo M: Multirresistencia a drogas (MDR) en oncología. An Med Interna 1997;14:145–153.
  3. Cos J, Bellmunt J, Ribas A, Lluis JM, Murio JE, Margarit C: Comparative study of sequential combinations of placlitaxel and methotrexate on a human bladder cell line. Cancer Invest 2000;18:429–435.
  4. Vezmar S, Becker A, Bode U, Jaehde U: Biochemical and clinical aspects of methotrexate neurotoxicity. Chemotherapy 2003;49:92–104.
  5. El Fadili A, Richard D, Kündig C, Ouellette M: Effect of polyglutamylation of methotrexate on its accumulation and the development of resistance in the protozoan parasite Leishmania. Biochem Pharmacol 2003;66:999–1008.
  6. Wielinga P, Hooijberg JH, Gunnarsdottir S, Kathmann I, Reid G, Zelcer N, Van der Born K, de Haas M, Van der Heijden I, Kaspers G, Wijnholds J, Jansen G, Peters G, Borst P: The human multidrug resistance protein MRP5 transports folates and can mediate cellular resistance against antifolates. Cancer Res 2005;65:4425–4430.
  7. Bertino JR, Lin J, Pizzorno G, Li WW, Chang YM: The basis for intrinsic drug resistance or sensitivity to methotrexate. Adv Enzyme Regul 1989;29:277–285.
  8. Ciaiolo C, Ferrero D, Pugliese A, Ortolano B, Borrione P, Pileri A: Modulation of in vitro chemosensitivity in acute myelogenous leukaemia cell line by GM-CSF: opposing effects observed with different cytotoxic drugs and time exposure. Leuk Res 1999;23:931–938.
  9. Sakurai H, Yasui H, Kunitomi K, Kamatari M, Kaneko N, Nakayama A: Effects of static magnetic field on dissolved oxygen levels in aqueous solutions containing copper (II), iron (II), and heme iron(III) complexes. Pathophysiology 2000;7:93–99.
  10. Botstein D, Fink GR: Yeast: An experimental organism for modern biology. Science 1988;240:1439–1443.
  11. Laqué-Rupérez E, Ruiz-Gómez MJ, de la Peña L, Gil L, Martínez-Morillo M: Methotrexate cytotoxicity on MCF-7 breast cancer cells is not altered by exposure to 25 Hz, 1.5 mT magnetic field and iron(III) chloride hexahydrate. Bioelectrochemistry 2003;60:81–86.
  12. Siede W, Friedl AA, Dianova I, Eckardt-Schupp F, Friedberg EC: The Saccharomyces cerevisiae Ku autoantigen homologue affects radiosensitivity only in the absence of homologous recombination. Genetics 1996;142:91–102.
  13. Friedl AA, Kiechle M, Fellerhoff B, Eckardt-Schupp F: Radiation-induced chromosome aberrations in Saccharomyces cerevisiae: influence of DNA repair pathways. Genetics 1998;148:975–988.
  14. Rutkowski S, Bode U, Deinlein F, Ottensmeier H, Warmuth-Metz M, Soerensen N, Graf N, Emser A, Pietsch T, Wolff JE, Kortmann RD, Kuehl J: Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med 2005;352:978–986.
  15. Whitehead VM, Shuster JJ, Vuchich MJ, Mahoney DH Jr, Lauer SJ, Payment C, Koch PA, Cooley LD, Look AT, Pullen DJ, Camitta B: Accumulation of methotrexate and methotrexate polyglutamates in lymphobasts and treatment outcome in children with B-progenitor-cell acute lymphobastic leukemia: a Pediatric Oncology Group study. Leukemia 2005;19:533–536.
  16. Gieringer JH, Wenz AF, Just HM, Daschner FD: Effect of 5-fluorouracil, mitoxantrone, methotrexate, and vincristine on the antibacterial activity of ceftriaxone, ceftazidime, cefotiam, piperacillin, and netilmicin. Chemotherapy 1986;32:418–424.
  17. Fraga CG, Oteiza PI: Iron toxicity and antioxidant nutrients. Toxicology 2002;180:23–32.
  18. Valko M, Morris H, Cronin MT: Metals, toxicity and oxidative stress. Curr Med Chem 2005;12:1161–1208.
  19. Carmine TC, Evans P, Bruchelt G, Evans R, Handgretinger R, Niethammer D, Halliwell B: Presence of iron catalytic for free radical reactions in patients undergoing chemotherapy: Implications for therapeutic management. Cancer Lett 1995;94:219–226.

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