Cyclooxygenase and Prostaglandin in Cancer

As we know, Cox converts arachidonic acid in the cell membrane to prostaglandin H2, the precursor of the final series-2 prostanoids such as PGE2, PGD2, PGF2, PGI2, and thromboxane A2. PGE2, one of the final products, is well known for its activities, such as softening the cervix, uterine contraction, inducing abortion, etc., in obstetric field [5]. However, the important thing is that PGE2 has recently been shown to have a strong relation with tumorigenesis in that it increases cell proliferation, angiogenesis and metastatic potential, and inhibits apoptosis and cellular immunity, which seem to be due to the increased expression of PGE2 by Cox-2 because excessive levels of PGE2 and Cox-2 are implicated in mediating several kinds of malignancies. However, we must also consider the Cox-2 activity in tumor tissue on its own without mediating prostaglandins. It can behave directly for tumorigenesis with activities similar to those mentioned above. For example, Cox-2 directly increases the intranuclear nuclear factorkB, which is the main stimulus for gene activation and replication, and forms endogenous mutagen, malondialdehyde, from arachidonic acid, which can cause a mutation of p53, and stimulates vascular endothelial growth factor for angiogenesis [6, 7]. 15-hy droxyprostaglandin dehydrogenase (15-PGDH) is supposed to degrade PGE2 selectively, and decreased expression of 15-PGDH might also be related with cancer as previously reported [8, 9]. As the author has mentioned, selective PGE2 inhibitors would work for the prevention or treatment of cancer if it developed. However, considering the direct effects of Cox-2 on carcinogenesis, cancer is unfortunately not that simple to get over. Therefore, selective PGE2 inhibitors will continue to be just one of many ordinary agents, but one that has a slight benefit in treating cancer. However numerous, these sorts of studies should form a basis for the future conquest of cancer.