Email updates

Keep up to date with the latest news and content from BMC Cancer and BioMed Central.

Open Access Highly Accessed Research article

Regular aspirin use and lung cancer risk

Kirsten B Moysich*, Ravi J Menezes, Adrienne Ronsani, Helen Swede, Mary E Reid, K Michael Cummings, Karen L Falkner, Gregory M Loewen and Gerold Bepler

BMC Cancer 2002, 2:31  doi:10.1186/1471-2407-2-31

PubMed Commons is an experimental system of commenting on PubMed abstracts, introduced in October 2013. Comments are displayed on the abstract page, but during the initial closed pilot, only registered users can read or post comments. Any researcher who is listed as an author of an article indexed by PubMed is entitled to participate in the pilot. If you would like to participate and need an invitation, please email info@biomedcentral.com, giving the PubMed ID of an article on which you are an author. For more information, see the PubMed Commons FAQ.

Reduced lung cancer incidence in aspirin users

Graham Caine   (2002-11-29 07:32)  University Dept of Medicine, Sandwell & West Birmingham NHS Trust, Birmingham B18 7QH, UK. email

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, 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 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.

References:

Boberg EW, Miller EC, Miller JA, Poland A, Liem A (1983). Strong 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 43: 5163-73.

Caine GJ, Kehoe ST, Lip GYH. The role of aspirin in carcinogenesis. Br J Cancer. 2002;87(11):1336-7.

Chou H-C, Lang NP, Kadlubar FF (1995). Metabolic activation of N-hydroxy arylamines and N-hydroxy heterocyclic amines by human sulphotransferase (s). Cancer Res 55: 525-9.

Coughtrie MWH (1996). Sulphation catalysed by the human cytosolic sulphotransferases – chemical defence or molecular terrorism? Hum Expl Toxicol 15: 547-55.

Grover PL (1986). Pathways involved in the metabolism and activation of polycyclic 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. Drug Metab Dispos 19:1071-9.

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 initiation of pancreatic ductal carcinogenesis by N-nitrosobis (2-oxopropyl) amine in hamsters. Carcinogenesis 16: 457-9.

Competing interests

None.

top

Post a comment