Prostaglandins, their inhibitors and cancer

Prostaglandins (PGs) and their analogs endoperoxides are a large series of compounds which mainly enhanced cancer development and progression, acting as cocarcinogens or tumor promoters, and having profound effects on carcinogenesis. Although PGs are ubiquitous tissue hormones exerting pleiotropic effects on cancer cells, their mechanism(s) of action at molecular and cellular levels are not yet elucidated. Autoradiographic, ultrastructural, antigenic, and cell surface studies revealed that PGs act namely by their specific receptors and by interfering with DNA, RNA and protein synthesis, cell membranes and cell communications. PGs also play a role in tumor immunology and transplantation, acting as immunomodulators. Prostaglandins exert their effects by autocrine and paracrine mechanisms similar to hormone-like substances, and hypophysectomy reduces some of their tumor-promoting effects. PGs may act synergistically with hormones, growth factors (GFs), and vitamins. Several drugs called PG-synthesis inhibitors or PG-antagonists are found to markedly inhibit the cyclooxygenase activity. Most of these PG-inhibitors (aspirin, ibuprofen, indomethacin, piroxicam, sulindac) or commonly called NSAIDs (nonsteroidal antiinflammatory drugs) also significantly inhibit cancer development and cancer progression, and are recently used in epidemiological studies for cancer prevention and treatment. Developing more active and less toxic NSAIDs, which can also more selectively inhibit PG synthesis, is a promising field in prostaglandin research.