Arsenic: an angiogenesis inhibitor?
Ian Cameron's letter presents some data which have been interpreted
as evidence that arsenic present in drinking water being carcinogenic.
A peptide trivalent arsenical inhibits tumor angiogenesis by
perturbing mitochondrial function in angiogenic endothelial cells,
angiogenesis being being considered necessary for significant tumour
growth (1). If the active ingredient in this compound is arsenic then one
might indeed expect the numbers of tumours to increase in those exposed to
arsenic in their drinking water, if as has been proposed tumours are
initiated by those cellular functions including DNA mis-match repair that
are compromised by an impairment of oxidative phosphorylation. One might
also expect, however, inhibition of angiogenesis upon which the growth of
tumours depends and, therefore, better outcomes than those with tumours
that did not have arsenic in their drinking water.
One might also expect other hypothetical benefits of angiogenesis
inhibitors, including regression of obesity and of atheroscelerotic
disease, in those exposed to arsenic in their drinking water. The net
effect might, however, depend upon the concetration of arsenic to which
subjects were exposed, concentrations in water in the wells rising above
600mcg/L on occasions.
If arsenic is indeed an angiogenesis inhibitor then epidemiological
studies in Bangladesh could yield important information about the longer
term benefits and risks of using angiogenesis inhibitors, such as that
which has just received FDA approval in the US, to treat patients with
cancers. They might also yield important information about the
prophylactic potential of angiogeneis inhibitors. This could be
particlarly important information for it is very likely that the newly
approved drug will soon be widely used in the treatment of cancers and
could easily become abused for inducing weight loss in the obese.
Don AS, Kisker O, Dilda P, Donoghue N, Zhao X, Decollogne S,
Creighton B, Flynn E, Folkman J, Hogg PJ. A peptide trivalent arsenical
inhibits tumor angiogenesis by perturbing mitochondrial function in
angiogenic endothelial cells.
Cancer Cell. 2003 May;3(5):497-509.
Competing interests: No competing interests