International Journal of Advanced Science and Research 13 International Journal of Advanced Science and Research ISSN: 2455-4227, Impact Factor: RJIF 5.12 www.newresearchjournal.com/science Volume 1; Issue 5; May 2016; Page No. 13-20 Selective administration of COX-2 inhibitors play potential role in prostate cancer management- An “In silico” analysis 1 Dr. Sukumar Roy, *2 Dr. Partha Majumder 1 Professor & Head, Department of Biomedical Engineering, Netaji Subhas Engineering College, Garia, Kolkata, India. 2 Biomedical Scientist & Systems Biologist, Former Principal Scientist ( Helix info systems, Chennai), Former Head of The Department of Department of Applied Biotechnology & Bioinformatics, Sikkim Manipal University, CC: 1637, Kolkata, India Abstract Tumorigenesis is a complex process, and understanding the mechanisms behind tumorigenesis is key to identifying effective targeted therapies. Prostaglandins are signaling lipophilic molecules derived from phospholipids that are involved in normal physiologic functions. However, overexpression of prostaglandins has been associated with tumorigenesis. Several epidemiologic studies have shown an inverse correlation between the incidence of colon cancer and the use of nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit prostaglandin synthesis. The NSAIDs target cyclooxygenases (COX), essential enzymes in prostaglandin production. Cyclooxygenase-2 (COX-2) is an inducible form of the enzyme that is usually not expressed in normal tissue. Because COX-2 is frequently overexpressed in premalignant lesions and neoplasms, specific COX-2 inhibitors have been investigated as chemoprevention and potential chemotherapeutic agents. There is now preclinical and early clinical data that suggest inhibitors of COX-2 may protect against colon, breast, lung, esophageal, and oral tumors. This paper will discuss evidence addressing the possible mechanistic contribution of COX-2 in tumorigenesis and will explore the link between COX-2 activity and carcinogenesis. The potential role of COX-2 inhibitors in the chemoprevention and treatment of various tumors will also be discussed. Clinical trials using targeted inhibitors of COX-2 will be critical in determining if COX-2 is a viable molecular target in cancer management. Keywords: Prostaglandins, cyclooxygenase (COX), apoptosis, angiogenesis, tumorigenesis Introduction Prostaglandins and their derivatives are signaling lipophilic molecules that are involved in diverse homeostatic and reactive functions, including platelet aggregation, clot formation, vasodilation, and gastric cytotoxic protection, as well as renal sodium and water balance. The first step in the synthesis of prostaglandins is the hydrolysis of membrane phospholipids to arachidonic acid by phospholipase A2.Arachidonic acid is then converted to an unstable product, prostaglandin G 2 , which is rapidly converted to prostaglandin H 2 by the peroxidase activity of a cyclooxygenase (COX). Prostaglandin H2 is converted by tissue-specific enzymes to other prostaglandins and thromboxanes. There are two isoforms of the COX enzyme encoded by two different genes. Cyclooxygenase-1 (COX-1) is a constitutive enzyme that is present in most normal tissues and mediates the synthesis of prostaglandins required for normal physiologic functions. The gene for COX-1 is on human chromosome 9 [1] . Cyclooxygenase-2 (COX-2) is an inducible form of the enzyme that is not normally detected in most tissues and is coded by a gene on human chromosome 1 [2] . Cyclooxygenase-2 is induced by cytokines, growth factors, tumor promoters, and carcinogens [3] . Cyclooxygenase-2 is also induced by several oncogenes, such as v-Src, v-Ha-ras, HER2/neu and Wnt [4-7] . Although prostaglandins are involved in many normal physiologic functions, these molecules—and the COX enzymes involved in prostaglandin production may also be involved in tumorigenesis. Indeed, there is evidence that prostaglandins may contribute to tumorigenesis by inhibiting the immune system, stimulating cell growth, enhancing angiogenesis, increasing mutagen production, enhancing cell invasion, or inhibiting apoptosis. In this article, we will discuss these mechanisms and will explore the role of COX-2 tumorigenesis. We will also review clinical trials that have investigated COX-2inhibitors as chemo protection agents and will discuss future directions in the study of COX-2 as a therapeutic target in cancer management. Mechanisms of Prostaglandins in Carcinogenesis Immunosuppressive Effects Prostaglandins have a variety of immunosuppressive effects. For example, prostaglandin E2 diminishes the cytotoxic activity of natural killer cells, inhibits T-cell and B-cell growth, and decreases the production of cytokines including tumor necrosis factor-alpha. Huang et al., [8] . showed that pretreatment with a prostaglandin inhibitor prevents an increase in interleukin-10 synthesis by peripheral blood lymphocytes. Furthermore, prostaglandins may also interfere with antigen processing by dendritic cells [9] . The ability of prostaglandins to inhibit the immune system may allow tumors to grow without surveillance and may contribute to tumorigenesis. Mitogenic Effects Enhanced prostaglandin synthesis may also contribute to tumorigenesis by direct stimulation of cell growth. Data have shown that prostaglandin E2 and prostaglandin F2-alpha can be Mitogenic in BALB/c3T3fibroblasts in the presence of epidermal growth factor [10] . Furthermore, proliferation of mammary epithelial cells can be stimulated in the presence of epidermal growth factor by prostaglandin E1 and prostaglandin