Chemopreventive effects of NSAIDs on cytokines and transcription factors during the early stages of colorectal cancer.
Journal Title: Pharmacological Reports - Year 2011, Vol 63, Issue 5
Abstract
The earliest stages of colorectal cancer have been linked to inflammatory responses caused by carcinogens, but the molecular signaling of various pro- and anti-inflammatory cytokines and transcription factors in colorectal cancer remains unknown. The higher expression and secretion of various pro-inflammatory cytokines and their autocrine and paracrine functions play an important role in the activation of transcription factors, which in turn promote tumorigenesis. NF-κB serves as a vital biomolecule that transcribes a number of pro-inflammatory cytokines and anti-apoptotic proteins. Pro-inflammatory cytokines can also activate Jak3/Stat3 signaling pathways, thereby increasing inflammation and cell survival. In the present study, the expression of IL-1β, IL-2, IL-4, IFNγ, TNF-α, iNOS, COX-2, Jak3, Stat3 and NF-κB were increased in the early stages of experimental colorectal cancer. The increased expression of these inflammatory molecules was reversed by the simultaneous administration of non-steroidal anti-inflammatory drugs (NSAIDs; sulindac and celecoxib). The anti-inflammatory activity of the NSAIDs was found to be mediated by the inhibition of NF-κB (p65) DNA-binding activity. The anti-neoplastic end effect of the NSAIDs in the isolated colonocytes was demonstrated by an increased level of apoptosis. This study suggests that NSAIDs inhibit NF-κB and Jak3/Stat3 signaling and down-regulate pro-inflammatory cytokines to a level that inhibits inflammation and carcinogenesis.
Authors and Affiliations
Vivek Vaish, Sankar Sanyal
Keywords
Related Articles
- EP ID EP103090
- DOI -
- Views 90
- Downloads 0
Growth hormone therapy in children and adults.
Growth hormone (GH) is a polypeptide hormone, secreted by somatotropic cells of the anterior part of the hypophysis. Its application in therapy, first limited to GH deficient children, has now been widened to various oth...
Influence of aripiprazole and olanzapine on behavioral dysfunctions of adolescent rats exposed to stress in perinatal period.
Background: Schizophrenia is a group of mental disorders of unclear origin, affecting around 1% of global population, most commonly young people. Of various treatment methods, pharmacotherapy using atypical neuroleptics...
Acute doxorubicin nephrotoxicity in rats with malignant neoplasm can be successfully treated with fullerenol C(60)(OH)(24) via suppression of oxidative stress.
Oxidative stress has an important role in the pathogenesis of doxorubicin (DOX)-induced nephrotoxicity. The aim of this study was to investigate the nephroprotective effects of fullerenol (FLR), an antioxidant agent, on...
Calcium mobilization by the plant estrogen ferutinin does not induce blood platelet aggregation.
Platelet activation is closely associated with an increase in intracellular Ca(2+) concentration. Various compounds including Ca(2+) ionophores are able to trigger platelet aggregation by increasing intracellular Ca(2+)...
Zinc and depression. An update.
Unsatisfactory clinical efficacy and a variety of adverse effects of current antidepressant drugs have incited search for better therapy. Zinc, an antagonist of the glutamate/N-methyl-D-aspartate (NMDA) receptor, exhibit...