A newly synthesized molecule derived from ruthenium cation, with antitumour activity, activates NADPH oxidase in human neutrophils

To determine the nature of the mechanism by which certain derived ruthenium (Ru) complexes induce regression in tumour growth, we have investigated the possibility that this mechanism was associated with an increase of superoxide anion (O2-. production by phagocytic cells, which are usually found in...

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Bibliographic Details
Published in:Biochemical journal 1997-12, Vol.328 ( Pt 2) (2), p.559-564
Main Authors: Carballo, M, Vilaplana, R, Márquez, G, Conde, M, Bedoya, F J, González-Vílchez, F, Sobrino, F
Format: Article
Language:English
Subjects:
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - pharmacology
Calcium - metabolism
Cations
Cell Compartmentation
Edetic Acid - analogs & derivatives
Edetic Acid - chemical synthesis
Edetic Acid - pharmacology
Enzyme Activation
Humans
Ion Transport
NADPH Oxidases - metabolism
Neutrophils - drug effects
Neutrophils - enzymology
Organometallic Compounds - chemical synthesis
Organometallic Compounds - pharmacology
Phosphorylation
Reactive Oxygen Species - metabolism
Respiratory Burst - drug effects
Tyrosine - metabolism
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Summary:To determine the nature of the mechanism by which certain derived ruthenium (Ru) complexes induce regression in tumour growth, we have investigated the possibility that this mechanism was associated with an increase of superoxide anion (O2-. production by phagocytic cells, which are usually found in tumour nodes. Here we present evidence that a newly synthesized complex, Ru3+-propylene-1, 2-diaminotetra-acetic acid (Ru-PDTA), derived from Ru and the sequestering ligand (PDTA), specifically stimulates O2-. production. This increase was associated with the translocation of cytosolic factors p47(phox) and p67(phox) of NADPH oxidase to the plasma membrane. The Ru-PDTA-complex-dependent O2-. production was abrogated by staurosporine, partially inhibited by diphenylene iodonium, and it was insensitive to pertussis toxin or dibutyryl cyclic AMP pretreatment. An increase of cytosolic Ca2+ levels were also detected in neutrophils treated with the Ru-PDTA complex. Also, Ru-PDTA complex induced the phosphorylation of tyrosine residues of several proteins as assessed by Western blotting. Present data are consistent with the possibility that Ru-PDTA-dependent antitumour effects are due in part to the complex's ability to stimulate the release of toxic oxygen metabolites from phagocytic cells infiltrating tumour masses.
ISSN:0264-6021
1470-8728
DOI:10.1042/bj3280559