title: Chemopreventive action of non-steroidal anti-inflammatory drugs on the inflammatory pathways in colon cancer.
abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are emerging as novel chemopreventive agents against a variety of cancers owing to their capability in blocking the tumor development by cellular proliferation and by promoting apoptosis. Inflammation is principal cause of colon carcinogenesis. A missing link between inflammation and cancer could be the activation of NF-κB, which is a hallmark of inflammatory response, and is commonly detected in malignant tumors. Therefore, targeting pro-inflammatory cyclooxygenase enzymes and transcription factors will be profitable as a mechanism to inhibit tumor growth. In the present study, we have studied the role of various pro-inflammatory enzymes and transcription factors in the development of the 1,2-dimethylhydrazine dihydrochloride (DMH)-induced colorectal cancer and also observed the role of three NSAIDs, viz., Celecoxib, Etoricoxib and Diclofenac. Carcinogenic changes were observed in morphological and histopathological studies, whereas protein regulations of various biomolecules were identified by immunofluorescence analysis. Apoptotic studies was done by TUNEL assay and Hoechst/PI co-staining of the isolated colonocytes. It was found that DMH-treated animals were having an over-expression of pro-inflammatory enzymes, aberrant nuclear localization of activated cell survival transcription factor, NF-κB and suppression of anti-inflammatory transcription factor PPAR-γ, thereby suggesting a marked role of inflammation in the tumor progression. However, co-administration of NSAIDs has significantly reduced the inflammatory potential of the growing neoplasm.
authors.affiliation: Department of Biophysics, Panjab University, Chandigarh 160014, India.
authors.forename: Preety
authors.initials: P
authors.lastname: Ghanghas
authors.affiliation: Department of Biophysics, Panjab University, Chandigarh 160014, India.
authors.forename: Shelly
authors.initials: S
authors.lastname: Jain
authors.affiliation: Department of Biophysics, Panjab University, Chandigarh 160014, India.
authors.forename: Chandan
authors.initials: C
authors.lastname: Rana
authors.affiliation: Department of Biophysics, Panjab University, Chandigarh 160014, India. Electronic address: sanyalpu@gmail.com.
authors.forename: S N
authors.initials: SN
authors.lastname: Sanyal
mesh_terms: D058739:Aberrant Crypt Foci / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D002469:Cell Separation; D018890:Chemoprevention; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000517:prevention & control*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000150:complications / Q000188:drug therapy*; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; D047495:PPAR gamma; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
keywords: Apoptosis; Colon cancer; Cyclooxygenase; DMH; NF-κB; NSAIDs