Prostaglandins, cancer inflammation

Prostaglandins (PG) and nitric oxide (NO) produced by inducible cyclooxygenase (COX-2) and nitric oxide synthase (iNOS), respectively, have been implicated as important mediators in the processes of inflammation and carcinogenesis. Potential COX-2 and iNOS inhibitors have been considered as anti-inflammatory and cancer chemopreventive agents [25]. 

In addition to inflammation, another potential role for natural COX and LOX dual inhibitors is in the prevention and treatment of cancers [80], Over expression of COX-2 has been demonstrated in various different human malignancies. COX-2 inhibitors have also been shown to be efficacious in the treatment of animal models of skin, breast and bladder tumors. While the mechanism of action remains to be completely defined, the over expression of COX-2, in excess of production of prostaglandin E2 and 5-hydroxyeicosatetraenoic acid (5-HETE) have been shown to inhibit apoptosis and increase the invasiveness of tumerogenic cell types [81,82]. It is probable that the enhanced production of PGE2 and 5-HETE promotes cellular proliferation, and consequently, increases angiogenesis [83]. 

The prostaglandins are lipid mediators implicated, not only in inflammation, but also, in other pathological processes, such as edema, fever, hyperalgia, cancer or Alzheimer s disease. The cyclooxygenase (COX) is the rate-limiting enzyme in the synthesis of PGE2, TXB2 and prostacyclines from arachidonic acid. 

Di Marzo, V., Melck, D., De Petrocellis, L, and Bisogno, T. (2000) Cannabimimetic fatty acid derivatives in cancer and inflammation. Prostaglandins and Other Lipid Mediators 61 43-61. 

Cyclo-oxygenase 2 (COX-2) has been proposed as a target for noninvasive imaging of inflammation and cancer. This is based on the notion that COX is the critical enzyme in prostaglandin synthesis. COX-2, a membrane-bound enzyme, has potent inflammatory effects but is also overexpressed in colon, breast, lung, and other cancers. COX-2 overexpression results in decreased apoptosis and increased cell migration and proliferation. 

The effects of co-3 and co-6 fatty adds in inflammation and aiitoimmnne diseases have been linked to the concentration of the type of prostaglandins and leukotrienes present in the cells. EPA-derived eicosanoids are less potent inducers of inflammation than the arachidonie aeid-derived eicosanoids, and competition between co-3 and co-6 fatty acids occurs in the prostaglandins formation. For instanee, an increased level of interleukin (IL) 1, a pro-inflamatory cytokine, is present in CHD, depression, aging, and cancer. Similarly, high levels of ILl and series-4 leukotrienes producod by co-6 fatty acids are presort in arthritis and other autoimmune diseases. 

---