tech: Aspirin and cancer

[Guest guest]

Hi All, I thought you might like the attached describing how aspirin may

inhibit cancer. It is a letter in response to a paper on aspirin in lung

cancer.

Cheers, Al.

BJC British Journal of Cancer 18 Nov 2002, 87, 11,

1337-1338.

The role of aspirin in carcinogenesis

G J Caine, S T Kehoe and G Y H Lip

We read with interest the excellent paper by

Akhmedkhanov

et al (2002) regarding aspirin use and the incidence

of

for 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 ( 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

Akhmedkhanov A, Toniolo P, Zeleniuch-Jacquotte A,

Koenig

KL, Shore RE. (2002). Aspirin and lung cancer in

women.

Br J Cancer, 87: 49-53. MEDLINE

Boberg EW, EC, 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: 5163-5173. MEDLINE

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: 525-529. MEDLINE

Coughtrie MWH. (1996). Sulphation catalysed by the

human

cytosolic sulphotransferases - chemical defence or

molecular terrorism? Hum Expl Toxicol, 15: 547-555.

Grover PL. (1986). Pathways involved in the

metabolism

and activation of polycyclic hydrocarbons.

Xenobiotica,

16: 915-931. MEDLINE

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: 1071-1079.

MEDLINE

Rao SI, Duffel MW. (1991). Inhibition of aryl

sulfotransferase by carboxylic acids. Drug Metab

Dispos,

19: 453-455.

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: 457-459. MEDLINE