How Aspirin Reduces Cancer Incidence by 40%
Aspirin works within the free radical framework
Free radical framework
in the interpretation that follows, aspirin works within the free radical framework. Simply put, a framework is like a sun glass colored green. All you see through this sun glass has the tinge of green. This framework involves free radicals and its derivatives called reactive oxygen species. These are singly or in combination used as independent variables in the conduct of scientific experiment.
Let us first see the context. The enzyme cyclooxygenase (COX) acts on arachidonic acid and produces prostaglandins. This consists of thromboxane and prostacyclin. The by-product of this reaction is superoxide, a free radical (Sears, B. Ph.D. The Zone. 1995).
COX consists of COX-1 and COX-2. These cause inflammation, ulcer, and pain among others. Thromboxane and prostacyclin are eicosanoids; but that is another story.
Thromboxane promotes aggregation of blood platelets that may result in clotting. Blood clot that lodges in occluded part of an artery, called plaque, lessens blood flow that may result in stroke or heart attack.
Prostacyclin does the opposite of thromboxane. It dilates arteries and promotes blood flow. It alleviates angina and prevents stroke and heart attack.
Now comes aspirin into the picture. Aspirin, as inhibitor, modifies COX-1; allows some production of thromboxane and prostacyclin. COX-2 completely blocks their production. So, no thromboxane and prostacyclin are produced. Also no superoxide is produced.
Aspirin is a COX-1 inhibitor that allows production of some thromboxane and prostacyclin that is why it can prevent heart attack. Prostacyclin is essential in the prevention of aggregation of blood platelet. By allowing a limited amount of superoxide it limits the population of superoxide that injure DNA that results in tumor and cancer. That is why aspirin also prevents to some degree cancer.
(I have a Hub on how pain relievers induce stroke and heart attack. I have several Hubs on free radicals.)
Research found that aspirin controlled cancer by 40%. That is, aspirin reduced the occurrence of cancer by 40% (Sears, 1995).
There is a side effect of blocking COX altogether for a long time. Arachidonic acid accumulates and becomes converted into leukotreine. This is a mediator of allergy. That is why a fellow who takes aspirin for a long time becomes allergic to any drug.
The above discussion also explains why a COX-2 inhibitor induces stroke or heart attack. This inhibitor blocks the production of thromboxane and prostacyclin. This was the case of Vioxx, a painkiller that also blocks COX-2. Vioxx was withdrawn from the market in 2004 by its maker, Merck company, when it found that it promotes stroke and heart attack when taken continuously in 18 months.
So far, the more extensive research on free radicals involve nitric oxide, a gas free radical produced by the inner wall of the artery (endothelium). We now know that the endothelium produces three kinds of nitric oxide (NO) depending on the kind of enzyme catalyzing the reaction.
The endothelium nitric oxidase (NOS) enzyme produces NO/eNOS. The inducible nitric oxidase produces NO/iNOS. The neuron nitric oxidase produces NO/nNOS. NO/eNOS is a free radical that signals the artery to dilate.
Research on nitric oxide was triggered by three Nobel Prize winners in medicine in 1998: Robert Futchgott, Ferid Murad and Louis Ignarro. Their work explain how nitroglycerin alleviates angina and prevent heart attack. For a long time nitroglycerin had been used for these purposes but its mechanism was unknown. Nitroglycerin (Imdur, Isordil) produces nitric oxide. An artery with plaque does not produce NO just when NO is needed to dilate it (Ornish, D. MD. Dr. Dean Ornish's Program for Reversing Heart Disease, 1996)..
Futchgott found that the endothelium produces a gas messenger that dilates the artery and called it endothelium-derived relaxation factor (EDRF). Later, Murad found that nitroglycerin produces nitric oxide. Then Ignarro found that EDRF and nitric oxide are the same.
However, there remained one question and that was: isn't it that free radicals are harmful? Later research on nitric oxide found that there are three kinds of nitric oxide. So, three categories emerged: free radicals (molecular oxygen, singlet oxygen, superoxide), reactive oxygen species (ROS) also called reactive oxygen intermediates (hydrogen peroxide, hydroxyl radical, alkoxy radical, lipid peroxide, peroxynitrite), and signal free radical (nitric oxide produced by the endothelium nitric oxidase). I have another Hub on this matter.
All three kinds are involved in heart disease and cancer. They are useful or harmful depending on their role. Free radicals and ROS initiate cancer. However, free radicals and ROS as active ingredients of chemotherapy drugs also kill cancer cells.
We need more research in the free radical framework, especially for heart disease and cancer, the number one and number two killers in the world .