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 93
- Downloads 0
Chemopreventive effects of NSAIDs on cytokines and transcription factors during the early stages of colorectal cancer.
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 colorect...
Properties of 3-methyl-TIQ and 3-methyl-N-propargyl-TIQ for preventing MPTP-induced parkinsonism-like symptoms in mice.
Background: Selegiline, a therapeutic drug for Parkinson's disease (PD), structurally resembles the endogenous parkinsonism-related compound 1,2,3,4-tetrahydroisoquinoline (TIQ). In the present study, we evaluated the ef...
Influence of ABCB1, CYP3A4*18B and CYP3A5*3 polymorphisms on cyclosporine A pharmacokinetics in bone marrow transplant recipients.
The aim of this study was to retrospectively evaluate the effect of polymorphisms in the CYP3A4, CYP3A5 and ABCB1 genes on the dose-adjusted concentration and dose requirement of cyclosporine A(CsA) in Chinese recipients...
New light on the anti-colitic actions of therapeutic aminosalicylates: the role of heme oxygenase.
Although a variety of pharmaceutical preparations of aminosalicylate are commonly used in the clinic for the control of inflammatory bowel disease, the mechanisms underlying their therapeutic actions remain unclear. Rece...
Introduction to in vitro estimation of metabolic stability and drug interactions of new chemical entities in drug discovery and development.
Determination of metabolic properties of a new chemical entity (NCE) is one of the most important steps during the drug discovery and development process. Nowadays, in vitro methods are used for early estimation and pred...