Kirsten B Moysich*, Ravi J Menezes, Adrienne Ronsani, Helen Swede, Mary E Reid, K M Cummings, Karen L Falkner, Gregory M Loewen and Gerold Bepler
Corresponding author: Kirsten B Moysich firstname.lastname@example.org
BMC Cancer 2002, 2:31 doi:10.1186/1471-2407-2-31
(2002-11-29 07:32) University Dept of Medicine, Sandwell & West Birmingham NHS Trust, Birmingham
B18 7QH, UK.
I read with interest the excellent paper by Moysich et al regarding aspirin use and
the incidence of lung cancer. I would like to offer another possible anti-cancer property
of aspirin, namely, the inhibition of phenolsulphotransferase (PST) activity (Caine
et al, 2002).
PSTs are found throughout the body but the bowel, liver and platelets are known to
contain particularly high activities of this enzyme. PSTs are cytosolic and exist
in two forms: (i) P-PST, which selectively sulphates micromolar concentrations of
phenols; and (ii) M-PST, which is similarly selective for aromatic amines.
The main function of this sulphation is to scavenge low concentrations of endogenous
and exogenous toxins from the body, but the lability of the phenolic sulphate-ester
bond means it is liable to cause the formation of electrophilic free radicals. These
react chemically with DNA which may cause mutations leading to neoplasia (Coughtrie,
Food cooking can result in a wide variety of mutagenic compounds, including polyaromatic
hydrocarbons and heterocyclic amines, especially if the food becomes charred when
grilled or barbequed. Certainly, several polyaromatic hydrocarbons have been shown
to be activated by hydroxylation to phenols followed by sulphation via P-PST to the
final mutagenic form (Grover, 1986). P-PST has also been found to be responsible for
the activation of heterocyclic amines by N-sulphation, for example, the bladder carcinogen
2-napthylamine (Hernandez et al, 1991) and a wide variety of carcinogenic N-hydroxy
arylamines (Chou et al, 1995).
Thus, inhibition of P-PST would block one route of activation for both main groups
of carcinogen found in food. Indeed, Rao et al (Rao et al, 1991) have shown that salicylic
acid, the initial breakdown product of aspirin, is a potent inhibitor of aryl sulphotransferase
IV (AST IV), at least in the rat – and AST IV is the rat equivalent of human
PST enzymes. Other studies (Boberg et al, 1983, Tsutumi et al, 1995) have also shown
that sulphotransferase inhibitors dramatically reduces the potency of sulphation activated
carcinogens in both mice and hamsters.
I would therefore suggest that the action of salicylic acid on P-PST, by preventing
the excessive activation of carcinogens, may represent another possible pathway by
which aspirin may reduce cancer risk.
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Caine GJ, Kehoe ST, Lip GYH. The role of aspirin in carcinogenesis. Br J Cancer. 2002;87(11):1336-7.
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and N-hydroxy heterocyclic amines by human sulphotransferase (s). Cancer Res 55: 525-9.
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hydrocarbons. Xenobiotica 16: 915-31.
Hernandez JS, Powers SP, Weinshilboum RM (1991). Human liver arylamine n-sulfotransferase
activity. Thermostable phenol sulfotransferase catalyzes the N-sulfation of 2-napthylamine.
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Rao SI, Duffel MW (1991). Inhibition of aryl sulfotransferase by carboxylic acids.
Drug Metab Dispos 19: 453-5.
Tsutumi M, Noguchi O, Okita S (1995). Inhibitory effects of sulfation inhibitors on
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