Abstract
British Journal of Cancer (2002) 87, 1337–1338. doi:10.1038/sj.bjc.6600670 www.bjcancer.com
Sir
We read with interest the excellent paper by Akhmedkhanov et al (2002) regarding aspirin use and the incidence of lung cancer. We would like to offer another possible anti-cancer property of aspirin, namely, the inhibition of phenolsulphotransferase (PST) activity.
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, 1996).
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 and Duffel (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.
We 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.
References
- AkhmedkhanovATonioloPZeleniuch-JacquotteAKoenigKLShoreRE2002Aspirin and lung cancer in women Br J Cancer 874953 [DOI] [PMC free article] [PubMed] [Google Scholar]
- BobergEWMillerECMillerJAPolandALiemA1983Strong evidence from studies with brachymorphic mice and pentachlorophenol: that 1′-sulfooxysafrole is the major ultimate electrophilic and carcinogenic metabolite of 1′-hydroxysafrole in mouse liver Cancer Res 4351635173 [PubMed] [Google Scholar]
- ChouH-CLangNPKadlubarFF1995Metabolic activation of N-hydroxy arylamines and N-hydroxy heterocyclic amines by human sulphotransferase(s) Cancer Res 55525529 [PubMed] [Google Scholar]
- CoughtrieMWH1996Sulphation catalysed by the human cytosolic sulphotransferases – chemical defence or molecular terrorism? Hum Expl Toxicol 15547555 [DOI] [PubMed] [Google Scholar]
- GroverPL1986Pathways involved in the metabolism and activation of polycyclic hydrocarbons Xenobiotica 16915931 [DOI] [PubMed] [Google Scholar]
- HernandezJSPowersSPWeinshilboumRM1991Human liver arylamine n-sulfotransferase activity. Thermostable phenol sulfotransferase catalyzes the N-sulfation of 2-napthylamine Drug Metab Dispos 1910711079 [PubMed] [Google Scholar]
- RaoSIDuffelMW1991Inhibition of aryl sulfotransferase by carboxylic acids Drug Metab Dispos 19453455 [PubMed] [Google Scholar]
- TsutumiMNoguchiOOkitaS1995Inhibitory effects of sulfation inhibitors on initiation of pancreatic ductal carcinogenesis by N-nitrosobis (2-oxopropyl) amine in hamsters Carcinogenesis 16457459 [DOI] [PubMed] [Google Scholar]