Summary
Good evidence indicates that the regular consumption of aspirin reduces the risk of colorectal cancer by up to 50%. This paper discusses mechanisms for this protection and considers carcinogen activation, cell proliferation, apoptosis and immune surveillance. It is not clear, however, whether these mechanisms are dose related. This question will remain to be answered until the optimum dose and duration of aspirin required for protection against colorectal cancer is established.
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References
International Agency for Research on Cancer (1997): IARC Handbooks of Cancer Prevention. Non-Steroidal Anti-Inflammatory Drugs, Lyon, International Agency for Research on Cancer, 1–202.
Marnett L.J., Kalgutkar A.S. (1998): Design of selective inhibitors of cyclooxygenase-2 as nonulcerogenic anti-inflammatory agents. Curr. Opin. Chem. Biol., 2, 482–490.
Eling T.E., Thompson D.C., Foureman G.L., Curtis J.F., Hughes M.F. (1990): Prostaglandin H synthase and xenobiotic oxidation. Annu. Rev. Pharmacol. Toxicol., 30, 1–45.
Marnett L.J. (1992): Aspirin and the potential role of prostaglandins in colon cancer. Cancer Res., 52, 5575–5589.
Marnett L.J. (1999): Lipid peroxidation-DNA damage by malondialdehyde. Mutat. Res., 424, 83–95.
Ji C., Rouzer C.A., Marnett L.J., Pietenpol J.A. (1998): Induction of cell cycle arrest by the endogenous product of lipid peroxidation, malondialdehyde. Carcinogenesis, 19, 1275–1283.
Oshima M., Dinchuk J.E., Kargman S.L. et al. (1996): Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell, 87, 803–809.
Shiff S.J., Koutsos M.I., Qiao L., Rigas B. (1996): Nonsteroidal antiinflammatory drugs inhibit the proliferation of colon adenocarcinoma cells: effects on cell cycle and apoptosis. Exp. Cell. Res., 222, 179–188.
Elder D.J., Hague A., Hicks D.J., Paraskeva C. (1996): Differential growth inhibition by the aspirin metabolite salicylate in human colorectal tumor cell lines: enhanced apoptosis in carcinoma and in vitro-transformed adenoma relative to adenoma relative to adenoma cell lines. Cancer Res., 56, 2273–2276.
Reddy B.S., Kawamori T., Lubet R.A., Steele V.E., Kelloff G.J., Rao C.V. (1999): Chemopreventive efficacy of sulindac sulfone against colon cancer depends on time of administration during carcinogenic process. Cancer Res., 59, 3387–3391.
Mahmoud N.N., Boolbol S.K., Dannenberg A.J. et al. (1998): The sulfide metabolite of sulindac prevents tumors and restores enterocyte apoptosis in a murine model of familial adenomatous polyposis. Carcinogenesis, 19, 87–91.
Elder D.J., Halton D.E., Hague A., Paraskeva C. (1997): Induction of apoptotic cell death in human colorectal carcinoma cell lines by a cyclooxygenase-2 (COX-2)-selective nonsteroidal anti-inflammatory drug: independence from COX-2 protein expression. Clin. Cancer Res., 3, 1679–1683.
Zhang X., Morham S.G., Langenbach R., Young D.A. (1999): Malignant transformation and antineoplastic actions of nonsteroidal antiinflammatory drugs (NSAIDs) on cyclooxygenase-null embryo fibroblasts. J. Exp. Med., 190, 451–459.
He T.C., Chan T.A., Vogelstein B., Kinzler K.W. (1999): PPARδ is an APC-regulated target of nonsteroidal anti-inflammatory drugs. Cell, 99, 335–345.
Daniel T.O., Liu H., Morrow J.D., Crews B.C., Marnett L.J., (1999): Thromboxane A2 is a mediator of cyclooxygenase-2-dependent endothelial migration and angiogenesis. Cancer Res, 59, 4574–4577.
Morin P.J., Vogelstein B., Kinzler K.W. (1996): Apoptosis and APC in colorectal tumorigenesis. Proc. Natl. Acad. Sci. USA, 93, 7950–7954.
Arvind P., Papavassiliou E.D., Tsioulias G.J. et al. (1995): Prostaglandin E2 down-regulates the expression of HLA-DR antigen in human colon adenocarcinoma cell lines. Biochemistry, 34, 5604–5609.
Arvind P., Papavassiliou E.D., Goldin E., Koutsos M.I., Rigas B., (1996): Aspirin and aspirin-like drugs induce the expression of HLA-DR in HT29 colon adenocarcinoma cells. Int. J. Oncol., 52, 237–245.
Rumore M.M., Aron S.M., Hiross E.J. (1987): A review of mechanism of action of aspirin and its potential as an immunomodulating agent. Med Hypoth., 22, 387–400.
Rigas B., Tsioulias G.J., Allan C., Wali R.K., Brasitus T.A. (1994): The effect of bile acids and piroxicam on MHC antigen expression in rat colonocytes during colon cancer development. Immunology, 83, 319–323.
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Vainio, H., Morgan, G. Mechanisms of aspirin chemoprevention of colorectal cancer. Eur. J. Drug Metab. Pharmacokinet. 24, 289–292 (1999). https://doi.org/10.1007/BF03190034
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DOI: https://doi.org/10.1007/BF03190034