Colon Cancer Stopped by Lipoxins and Resolvins: Aspirin Targets Cyclooxygenase-2 (COX-2) for Treatment

Inflammation is a critical process of most cancers, since the same transcription factor, NF-kappaB, controls both inflammation and cancer proliferation. Both bacteria and cancer cells activate NF-kappaB and stimulate the expression of inflammatory proteins, such as inflammatory cytokines (IL-1, IL-6, TNF), enzymes (e.g. COX-2) to produce inflammatory prostaglandins, and enzymes that regulate blood flow (e.g. iNOS that produces nitric oxide, NO). Thus, the redness, swelling and pain that is identified as tissue inflammation, is frequently also associated with cancers. Aspirin, which is used as a traditional treatment for inflammation, has recently been identified as a potent treatment for cancer.

COX-2 Produces Prostaglandins

The major health risk associated with polyunsaturated vegetable oils, e.g. corn and soy oils, is that they contain omega-6 fatty acids that can be converted by COX-2 into prostaglandins that are inflammatory. Similarly, COX-2 acts on omega-3 fatty acids from fish oils and converts them into anti-inflammatory prostaglandins. This is why the ratio of omega-6 to omega-3 fatty acids in a Western diet is associated with inflammation and degenerative diseases.

Aspirin Inhibits COX-2 Production of Inflammatory Prostaglandins

Aspirin decreases inflammation partly by inhibiting COX-2 activity and reducing the production of inflammatory prostaglandins. Unfortunately, the gut needs these same prostaglandins for proper development and to maintain its integrity. Thus, it is recommended to take aspirin tablets with large quantities of water to avoid problematic concentrations of aspirin in a single localized region that would result in leakage of bacteria into the surrounding tissue and into blood vessels that lead to the liver.

Aspirin Modifies COX-2 to Produce Anti-inflammatory Lipoxins and Resolvins

Inflammation is a sequential process that normally leads to its own resolution. Inflammatory signals naturally trigger the production of anti-inflammatory signals to return to the initial conditions. Aspirin also mediates this resolution process by chemically altering, acetylating, the COX-2 to change its enzyme activity. The acetylated COX-2 converts omega-6 fatty acids into alternative, anti-inflammatory lipoxins and resolvins, that promote a return to normal tissue function and reduce inflammation.

Aspirin Blocks COX-2 Proliferation of Colon Cancer

The anti-inflammatory production of lipoxins and resolvins leads to a reduction in the activity of the inflammatory transcription factor, NFkappaB. Proliferation of cancers of all types requires the activity of NFkappaB to express genes needed for metastasis and to prevent death, apoptosis, of the unregulated tumor cells. As might be expected, the reduced activity of NFkappaB also blocks the proliferation of cancer. In recent experiments, aspirin was effectively used to reduce colon cancer proliferation and growth.