Effects of agents that inhibit cellular iron incorporation on bladder
cancer cell proliferation
PA Seligman, RB Schleicher, G Siriwardana, J Domenico and EW Gelfand
Department of Medicine, University of Colorado Health Sciences Center,
Denver 80262.
Agents that interfere with cellular iron (Fe) incorporation inhibit tumor
cell proliferation, including metals that bind to transferrin (Tf) such as
gallium (Ga) or indium (In) and Fe chelators such as desferrioxamine (DFO).
Ga nitrate is effective in the treatment of metastatic bladder cancer and
these patients exhibit evidence for interference with Fe metabolism. We
show here that bladder cancer cell proliferation in vitro is dependent on
Tf-Fe. Concentrations of DFO that can be readily achieved in vivo inhibit
cellular proliferation even in the presence of physiologic concentrations
of Tf-Fe. Inhibition of proliferation by Tf-Ga is associated with decreased
cellular Fe incorporation. However, when a physiologic concentration of
Tf-Fe is added to an equimolar concentration of Tf-Ga, significant Fe
incorporation is evident despite inhibition of proliferation. Thus, besides
interference with Fe incorporation, Ga may also interfere with
intracellular Fe distribution and/or directly inhibit an Fe- (or non-Fe- )
requiring process necessary for cellular proliferation. DFO followed
sequentially by Tf-Ga results in marked potentiation of inhibition of
proliferation. The effects of this combination appear to be related to both
interference with Fe metabolism and increased Ga uptake. This sequential
combination may be useful in the treatment of bladder cancer.
Volume 82,
Issue 5,
pp. 1608-1617,
09/01/1993
Copyright © 1993 by The American Society of Hematology
