Non-steroid anti-inflammatory drugs, prostaglandins, and cancer

Abstract

Fatty acids are involved in multiple pathways and play a pivotal role in health. Eicosanoids, derived from arachidonic acid, have received extensive attention in the field of cancer research. Following release from the phospholipid membrane, arachidonic acid can be metabolized into different classes of eicosanoids through cyclooxygenases, lipoxygenases, or p450 epoxygenase pathways. Non-steroid anti-inflammatory drugs (NSAIDs) are widely consumed as analgesics to relieve minor aches and pains, as antipyretics to reduce fever, and as anti-inflammatory medications. Most NSAIDs are nonselective inhibitors of cyclooxygenases, the rate limiting enzymes in the formation of prostaglandins. Long term use of some NSAIDs has been linked with reduced incidence and mortality in many cancers. In this review, we appraise the biological activities of prostanoids and their cognate receptors in the context of cancer biology. The existing literature supports that these lipid mediators are involved to a great extent in the occurrence and progression of cancer.

Figure 1

Biosynthesis and activities of prostaglandins and sites of NSAIDs actions. Cyclooxygenase metabolism of arachidonic acid can lead to the formation of prostaglandins that exert a variety of biological activities through their respective cognate receptors. The involvement of prostanoid receptors in cancer is also shown. Abbreviations: COX, cyclooxygenase; PG, prostaglandin; PLA₂, phospholipase 2; TXA₂, thromboxane A₂; TP, thromboxane A₂ receptor; EP, prostaglandin E₂ receptor; IP, prostacyclin (PGI₂) receptor; DP, prostaglandin D₂ receptor; FP, prostaglandin F₂ receptor; NSAIDs, non-steroid anti-inflammatory drugs.