The role of NF-κB and PPARγ in experimentally induced colorectal cancer and chemoprevention by cyclooxygenase-2 inhibitors.

Abstract

Initiation of malignancy is dependent upon the basic ratio of cell proliferation and apoptosis. Many molecular proteins and pathways are responsible for the imbalance of proliferation and apoptosis ratio. For example, Akt is a key biomolecule which regulates the cell survival signals via various downstream pathways. One of those pathways is nuclear factor-κB activation which also regulates many downstream pathways that are essential for cell survival. Along with these anti-apoptotic pathways, cells do have a parallel mechanism to prevent malignancy with the help of the ligand-induced nuclear receptors, e.g., peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ has been found to be expressed in many cancer cell types and reported to be a pro-apoptotic transcription factor. The study aimed to observe the ability of two cyclooxygenase-dependent non-steroidal anti-inflammatory drugs (NSAIDs) in the prevention of experimentally induced early neoplasm of colon via NF-κB and PPARγ pathways. Early stages of colorectal cancer were produced in rats with 1,2-dimethylhydrazine dihydrochloride. Western blotting and immunohistochemistry were performed along with morphological and histological analysis. According to the expression levels of NF-κB and PPARγ in the cell nuclei, it is observed that NSAIDs may prevent colorectal cancer in the early stages by a concomitant down-regulation of NF-κB and up-regulation of PPARγ. COX-independent mechanism of anti-carcinogenesis was observed by COX-dependent NSAIDs in colorectal cancer.

• Authors: Vivek Vaish, Lalita Tanwar, Sankar Nath Sanyal
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 31 Issue 5 Pg. 427-36 (Oct 2010) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 20514536 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Cyclooxygenase 2 Inhibitors
• NF-kappa B
• PPAR gamma
• Pyrazoles
• Sulfonamides
• Diclofenac
• Celecoxib

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)
• Blotting, Western
• Celecoxib
• Colorectal Neoplasms (chemically induced, metabolism, pathology, prevention & control)
• Cyclooxygenase 2 Inhibitors (therapeutic use)
• Diclofenac (therapeutic use)
• Immunohistochemistry
• Male
• NF-kappa B (metabolism)
• PPAR gamma (metabolism)
• Pyrazoles (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Sulfonamides (therapeutic use)