title: Chemopreventive effects of NSAIDs on cytokines and transcription factors during the early stages of colorectal cancer.
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.affiliation: Department of Biophysics, Panjab University, Chandigarh 160014, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Vaish
authors.forename: Sankar N
authors.initials: SN
authors.lastname: Sanyal
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018890:Chemoprevention / Q000379:methods; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D015179:Colorectal Neoplasms / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D014157:Transcription Factors