Natural Salicylates (aspirin) and the Cycloxidase pathway

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Over the last few years there has been great excitement and interest shown in an enzyme called Cyclo-oxidase which is modified by dietary salicylates and has been strongly implicated in the cancer pathway.
The initial interest in the anticancer properties of salicylates, or the most widely available type, aspirin (acetyl-salicylate) came from two sources. First, it was discovered via questionnaire surveys that people who took aspirin regularly seemed to have a lower incidence of cancer. The most notable of these was the Health Professionals Follow-up Study (HPFS) cohort at Harvard, which reported a decreased risk of advanced prostate cancer among men with regular aspirin use.

 Secondly, in laboratory experiments, when salicylates where added to cancer cells grown or given to animals with cancers, there was a significant reduction in their growth and rate of spread. Further experiments have shown similar affects with other aspirin like compounds including anti-inflammatory drugs known as non steroidal anti-inflammatory (NSAID). This family of drugs exert their anticancer properties via the cyclo-oxidase-2 (COX-2) protein. This protein is known to thrive on the surface of many types of cancer cells including those from prostate, breast, ovary and bowel. In general the higher the concentration (over expression) of this protein the more aggressive the cancer and the higher chance of it invading adjacent structures and spreading to organs of the body. More importantly the expression increases when a slow growing (indolent) tumour mutates into a more aggressive type. Salicylates inhibit the function of the COX-2 protein and therefore potentially prevent early cancers growing, becoming more aggressive, invading or spreading to other organs.  For this reason salicylates or NSAID are often referred to as COX-2 inhibitors. Normal cells do not over express COX-2 so in affect salicylates could specifically target the cancer cells and avoid the normal ones – the panacea for all anticancer strategies!

 Not surprising, in view of this theoretical and laboratory background numerous studies were conducted and published using salicylates or NSAID’s in patients with cancer. These however have mainly been designed to see if they helped prevent cancer coming back after initial treatment rather than a direct treatment in itself. They have also tended to use the newer highly selected NSAID known as pure COX-2 inhibitors which are thought to avoid the unwanted gastro-intestinal side effects whilst amplifying the anti-cancer COX-2 effects.

 The benefits of these pure COX-2 inhibitors over natural salicylates, those in tablet form or those found naturally within the diet have not however been established. Concerns have also arisen with the safety of some pure COX-2 inhibitors. First, the reduction in gastrointestinal side effects of pure COX-2 inhibitors have not been as strong as expected when tested clinically and indigestion and gastric damage remains high. Second, pure COX-2’s adversely affect the blood pressure and following long term use can affect the kidney. Third, most of the prospective studies so far, have actually shown a reduced incidence of malignancy associated with aspirin rather than other more pure NSAID. Fourth, the only prospective randomised clinical studies in oncology published to date showing a protective benefit against recurrent bowel cancer used aspirin. Finally the cardiac safety of some third generation NSAID has more recently been put in doubt with some trials actually showing an increased death rate caused by heart attacks. The answer, as is often the case may lie in nature; people with diets rich in fruit and vegetables, particularly vegetarians have serum salicylate equivalent to a dose of up to 80mg a day – usually more than enough to initiate COX-2’s likely biochemical anti-cancer process (conversion of arachidonic acid to prostaglandins). Higher intake of fruit and vegetables, as well as numerous other health benefits, actually protects the stomach and digestive pathway, lowering the risk adverse gastrointestinal symptoms such as indigestion. Every few months, as further confirmatory study data matures, there is a front page headline;

“Aspirin cuts cancer risk” Unfortunately our quest for quick fix tablets this makes these headlines interesting and eye catching. The alternative would hardly sell papers – read all about it:

“Fruit and vegetable cuts the cancer risk”

There is much we still do not know about the full benefits of COX-2 inhibition and a number of interesting trials are ongoing amoung patients with established cancer. A measure of COX-2 over expression on cancer cells and its inhibition within further dietary intervention studies would be useful. It would be particularly interesting to compare improved diet with salicylate supplementation but for these reasons described in chapter x this would be difficult to design and as it has no commercial interest, unlikely to attract funding.

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