Aspirin, salicylates and cancer
School of Medicine, Cardiff University, Cardiff, UK. The Lancet
(Impact Factor: 45.22).
04/2009; 373(9671):1301-9. DOI: 10.1016/S0140-6736(09)60243-9
Evidence from a wide range of sources suggests that individuals taking aspirin and related non-steroidal anti-inflammatory drugs have reduced risk of large bowel cancer. Work in animals supports cancer reduction with aspirin, but no long-term randomised clinical trials exist in human beings, and randomisation would be ethically unacceptable because vascular protection would have to be denied to a proportion of the participants. However, opportunistic trials of aspirin, designed to test vascular protection, provide some evidence of a reduction in cancer, but only after at least 10 years. We summarise evidence for the potential benefit of aspirin and natural salicylates in cancer prevention. Possible mechanisms of action and directions for further work are discussed, and implications for clinical practice are considered.
Available from: Gang Xie
- "Compelling evidence has emerged that non-steroidal anti-inflammatory drugs (NSAIDs) can reduce the incidence of various cancers and limit metastatic disease (1–3). However, the chronic use of NSAIDs is associated with significant gastrointestinal and renal toxicities. "
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ABSTRACT: Phospho-sulindac (PS) is a safe sulindac derivative with promising anticancer efficacy in colon cancer. We evaluated whether its combination with curcumin could enhance the efficacy in the treatment of lung cancer. Curcumin, the principal bioactive component in turmeric, has demonstrated versatile capabilities to modify the therapeutic efficacy of a wide range of anticancer agents. Here, we evaluated the effect of co-administration of curcumin on the anticancer activity of PS in a mouse xenograft model of human lung cancer. Curcumin enhanced the cellular uptake of PS in human lung and colon cancer cell lines. To assess the potential synergism between curcumin and PS in vivo, curcumin was suspended in 10% Tween-80 or formulated in micellar nanoparticles and given to mice by oral gavage prior to the administration of PS. Both formulations of curcumin significantly improved the pharmacokinetic profiles of PS, with the 10% Tween-80 suspension being much more effective than the nanoparticle formation. However, curcumin did not exhibit any significant modification of the metabolite profile of PS. Furthermore, in a mouse subcutaneous xenograft model of human lung cancer, PS (200 mg/kg) in combination with curcumin (500 mg/kg) suspended in 10% Tween-80 (51% inhibition, p<0.05) was significantly more efficacious than PS plus micelle curcumin (30%) or PS (25%) or curcumin alone (no effect). Consistent with the improved pharmacokinetics, the combination treatment group had higher levels of PS and its metabolites in the xenografts compared to PS alone. Our results show that curcumin substantially improves the pharmacokinetics of PS leading to synergistic inhibition of the growth of human lung cancer xenografts, representing a promising drug combination.
Available from: Iain D. Nicholl
- "Because of the intrinsic anti-inflammatory activity of NSAIDs a significant number of researchers have focused on this aspect as a protective mechanism. For example, aspirin can acetylate the cyclo-oxygenases (COX) significantly reducing arachidonic acid metabolism and prostaglandin production, thereby reducing inflammation (Elwood et al., 2009). Expression of the inducible COX, cyclooxygenase-2 is notably elevated in colorectal malignancies and in other cancers (Ferrandez et al., 2003; Kutchera et al., 1996; Soslow et al., 2000), and this overexpression has been actively implicated in the metastasic potential of tumours (Jang et al., 2009; Tsujii et al., 1997). "
Available from: Lesley A Anderson
- "In addition, our analysis revealed a slight, non-significant, reduction in HNC risk with increased frequency of ibuprofen use, suggesting a possible causal effect. Alternatively, aspirin may exert different COX-2 independent effects on reducing cancer compared with ibuprofen (Elwood et al, 2009). A greater reduction in HNC risk was observed with weekly/monthly aspirin use than daily use. "
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Evidence for non-steroidal anti-inflammatory drugs (NSAIDs) preventing head and neck cancer (HNC) is inconclusive; however, there is some suggestion that aspirin may exert a protective effect.
Using data from the United States National Cancer Institute Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, we examined the association between aspirin and ibuprofen use and HNC.
Regular aspirin use was associated with a significant 22% reduction in HNC risk. No association was observed with regular ibuprofen use.
Aspirin may have potential as a chemopreventive agent for HNC, but further investigation is warranted.
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