Cancer is one of those things that people like to talk about “curing”, but the reality is always much more complicated than that. There are many different kinds of cancer, and each type (colon, prostate, breast, etc) can have many different subtypes. It seems that we may never come up with an approach that will successfully treat them all. But at its base, cancer is all about one thing: unregulated cell proliferation. This means that cells divide when they are not supposed to, forming masses and invading areas where they are not supposed to be. So some areas of cancer research have focused on simply inhibiting unregulated cell proliferation, in the hopes that this can be further refined and targeted to be eventually used in cancer.
Amissah et al. “Celecoxib preserves arachidonic acid-induced cell degeneration: implications for the anticancer effects of NSAIDs and polyunsaturated fatty acids” Florida A&M University, presented at Experimental Biology, 2011.
When most people think of polyunsaturated fatty acids, they often think of things like omega-3s. Recent research has shown that polyunsaturated fatty acids of some kinds (like omega-3s) are good for you. From research on the Inuit tribe of Greenland (Dyerberg, 1975), who have a large amount of polyunsaturated fatty acids in their diets, scientists have found that they have a low incidence of cardiovascular disease, as well as a lower incidence of cancers. So scientists have been looking in to how these polyunsaturated fatty acids might work in certain areas of human health.
The hypothesis about polyunsaturated fatty acids as applied to cancer is that these acids are “pro-apoptotic”, encouraging cell death, which means that they can help check the progression of cancerous cells which are dividing when they shouldn’t be.
So these authors are looking at how to increase polyunsaturated fatty acids in cells that are dividing out of control, in order to induce cell death. In particular, they think that polyunsaturated fatty acids inhibit an enzyme known as PMPMEase (Polyisoprenylated Methylated Protein Methyl Esterase). PMPMEase is an enzyme which can increase cell proliferation. In cells that are already able to proliferate out of control, this is a definite problem. So the goal is to inhibit PMPMEase, to try and limit cell proliferation and induce cell death.
To look at how PMPMEase could be regulated by polyunsaturated fatty acids, they examined how well PMPMEase was inhibited by various types of fatty acid. It turns out that many unsaturated fatty acids could inhibit PMPMEase in vitro, but the best by far was arachidonic acid. Arachidonic acid is one of our essential fatty acids, and though it may have gotten a bad rap in the past, it is not known to be particularly harmful. And it turned out that when they applied arachidonic acid to cell cultures to inhibit PMPMEase, they got increases in cell death. When you’re trying to inhibit cell proliferation, that’s a pretty good thing.
But how do we know that arachidonic acid is inhibiting PMPMEase specifically? In this case, the scientists applied arachidonic acid, and then lysed the cells, and used high performance liquid chromatography to determine that PMPMEase was decreasing in a dose dependent manner as arachidonic acid levels increased.
And here’s where we get to something particularly interesting, the involvement of COX. COX stands for cyclooxygenase, and there are two types (COX 1 and COX 2). COX is an enzyme in the arachidonic acid PATHWAY, which breaks down arachidonic acid.
(Via Wikipedia)
You can see COX 1 and 2 sitting on the arrow just below arachidonic acid, converting it to prostaglandin. So the idea here is that, if arachidonic acid is really the mediator of the actions of PMPMEase, if you use COX 1 or 2 to inhibit arachidonic acid, you’ll recover PMPMEase activity and prevent cell death. And sure enough, this worked.
So what does all of this rather convoluted pathway stuff mean? It means that, at some point down the line, we may be able to use arachidonic acid in a targeted manner (because all of these acids and enzymes occur everywhere in the body) to inhibit PMPMEase in cancer cells to promote cell death. And to increase arachidonic acid, we will need to inhibit COX 1 and 2. Luckily, we HAVE drugs that inhibit COX 1 and 2, drugs like Celacoxib (which has some unfortunate side effects which could make it difficult to work with), and ASPIRIN. This seems like an even better idea when you know that cancer cells in particular have high levels of both PMPMEase and COX-2, which both increase cell proliferation. So the more we can inhibit the actions of PMPMEase and COX-2 in cancer cells, the better off we’ll be. Now it’s a matter of getting it from a dish and a pathway to a targeted drug and treatment. It may be many years down the line, and along the way we may learn many things we don’t know, things that could make this treatment incredibly useful or completely useless. But a pathway is always a start.
