br LOX in colorectal cancer Colorectal cancer CRC like other

5-LOX in colorectal cancer Colorectal cancer (CRC) like other malignancies exhibits an overexpression of 5-LOX. Ohd et al. (Ohd et al., 2003) revealed in a study that malignant colon tissues overexpress 5-LOX activity and retain elevated levels of inflammatory mediators, leukotrienes. Additionally, patients with high 5-LOX and LT receptor levels exhibited poor survival rates (Matsuyama et al., 2007). A potential mechanism for 5-LOX and its metabolites to control CRC cell growth is through its electrophilic activity and generation of reactive lipid metabolites that can disturb the translocation of p53 (transcription factor) to the nuclei (Bortuzzo et al., 1996). The mechanism that inhibits p53 accumulation by electrophiles could represent a pathway by which 5-HETE, LTs, and Nystatin receptor suppress apoptosis in CRC patients (Bortuzzo et al., 1996). Many 5-LOX inhibitors that have anti-tumor properties have been studied extensively and have been known for suppressing tumor growth in vivo murine models (Hussey and Tisdale, 1996). The combined suppression of 5-LOX and COX-2 is known for suppressing CRC cell proliferation and tumor metastasis, which is induced by tobacco exposure (Ye et al., 2005). 5-LOX inhibition was found to decrease DNA replication in a time and dose dependent way in the human CRC cell lines and reduce tumor growth in the animal models (Ye et al., 2005). 5-LOX inhibitor, Rev-590 showed strong chemo-preventive activity against CRC xenografts (Ye et al., 2005). These investigations support the assumption that 5-LOX is an important target molecule since 5-LOX inhibition prevents the proliferation of CRC cell lines and offer a favorable chemo-preventive therapy in CRC patients (Melstrom et al., 2008). Regulating 5-LOX activities by using natural agents have also shown some promising anti-cancer effects in CRC cases. The formation of 5-HETE was drastically suppressed by curcumin in the colon mucosa and tumors of rat models (Yasui et al., 2009). in vitro studies involving human CRC cell lines also showed the effective inhibition of 5-LOX activity by curcumin (Rao, 2007) and confirmed the natural agent’s anti-cancer effects. Phenolic constituents of honey, phenylethyl caffeate (PEC), and phenylethyl-3-methyl caffeate (PEMC) leads to significant inhibition of CRC cell line proliferation by decreasing the AA metabolism and suppressing the formation of 5-LOX metabolites such as 5-HETE (Rao et al., 2012). Therefore, these results indicate that caffeic acid esters display anti-inflammatory properties by suppressing 5-LOX pathways. Chebulagic acid (derived from the extracts of Terminalia chebula fruits) also showed important dual inhibiting action against 5-LOX and COX−2 as well as anti-proliferative activity (Reddy et al., 2009). Many dual inhibitors have been developed in recent years by using COX-2 and 5-LOX in order to avoid the toxicity of NSAIDs in treating gastrointestinal cancers. For example, licofelone (ML3000), an innovative dual 5-LOX/COX inhibitor, suppresses 5-LOX and COX activities and displays anti-inflammatory, analgesic, and antipyretic effects at a certain dose that has no toxicity and causes absolutely no gastrointestinal damage as compared to NSAIDs (Tavolari et al., 2008). Overall, the action of COX-2 and 5-LOX in CRC development are becoming well recognized and targeting these signaling pathways is a novel strategy for preventing and treating CRC.
Acknowledgements Aramati acknowledges DBT-RGYI and DST-SERB for funding,
Introduction Inflammation is a complex and well-regulated process critical for life and for the maintenance of the body and tissue homeostasis. However, inflammatory reactions when excessive or unresolved can also lead to deleterious consequences. Inflammatory mediators are capable of inducing signs of inflammation, such as the attraction and accumulation of immune cells and the loss of plasma from small vessels into the interstitial space in inflamed tissue [1]. The main task of the immune system is to protect the body against the invasion of pathogens. It is a complex network of regulators that controls the balance between defense and tolerance. The alteration of this network leads to the development of chronic inflammation, such as allergies, autoimmune reactions and infections. Human body to defend itself against pathogens develops innate and adaptive immune responses [2].