Biological activity of metal-edds (ethylenediaminedisuccinate) complexes in K562 and PBMC cells

Journal of the Brazilian Chemical Society

Natália J. S. Costa²  Szulim B. Zyngier¹  Cíntia R. Bombardieri¹  Juliana S. Kuribayashi¹  Maristela M. De Camargo¹  Breno P. Espósito² 

[1] ,Universidade de São Paulo Instituto de Química São Paulo SP ,Brazil

关键词: K562;    edds;    antitumor;    pro-oxidant;    cell cycle;    PBMC;   

DOI  :  10.1590/S0103-50532008000100018

来源: SciELO

【 摘 要 】

The effect of S,S-ethylenediaminedisuccinic acid (edds) on the quenching of metal-catalyzed (metal = Mn, Fe, Co, Ni, Cu, Zn) oxidation of ascorbic acid was tested in vitro via oxidation of the fluorescent probe 1,2,3-dihydrorhodamine dihydrochloride. The pro-oxidant activity of iron was not fully suppressed, even at a four-fold molar excess of the ligand. The effect of serum on the toxicity to peripheral blood mononuclear cells (PBMC) and K562 cells was investigated. The cytotoxic effect of Fe-edds was abrogated in the presence of Trolox or serum proteins. The probable pathways of cell toxicity were investigated through blocking of the monocarboxylate transporters (MCT) in association with cell cycle studies by flow cytometry. Cells treated with metal complexes and alpha-cyano-4-hydroxycinnamic acid, a known MCT inhibitor, showed recovery of viability, suggesting that MCT proteins may be involved in the internalization of metal-edds complexes. The free acid induced cell cycle arrest in G0/G1 (PBMC) and S (K562) phases, suggesting direct DNA damage or interference in DNA replication.

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