Arthur W Bull1. 1. Department of Chemistry, Oakland University, Rochester, Mich 48309-4477, USA. abull@oakland.edu
Abstract
OBJECTIVE: Review the role and therapeutic potential of peroxisome proliferator-activated receptor (PPAR) gamma in colonic disorders. DATA SOURCES: Recent peer-reviewed scientific literature focusing on PPAR gamma in the colon. STUDY SELECTION: Research reports using animal models, cultured cell lines, and clinical material were examined for content related to the role of PPAR gamma in normal colon cell function, colon cancer, and inflammatory bowel disease. Issues concerned with potential therapeutic use were also considered. DATA SYNTHESIS: Key points pertaining to PPAR function and involvement in colon pathology were extracted and noted. Potential compromises to therapeutic utility are identified. CONCLUSIONS: The emerging important role of PPAR gamma in normal tissue homeostasis and pathologic outcomes suggests this receptor is a good candidate as a drug target. Several potential problems with this approach will require further investigation prior to widespread recommendations for modulation of PPAR as an efficacious therapy for cancer, chemoprevention of colon cancer, or treatment of inflammatory bowel disease. The widespread use of PPAR gamma ligands for management of type 2 diabetes (such as the glitazone class of drugs including rosiglitazone and pioglitazone) may provide a fortuitous assessment of the efficacy of long-term PPAR modulation.
OBJECTIVE: Review the role and therapeutic potential of peroxisome proliferator-activated receptor (PPAR) gamma in colonic disorders. DATA SOURCES: Recent peer-reviewed scientific literature focusing on PPAR gamma in the colon. STUDY SELECTION: Research reports using animal models, cultured cell lines, and clinical material were examined for content related to the role of PPAR gamma in normal colon cell function, colon cancer, and inflammatory bowel disease. Issues concerned with potential therapeutic use were also considered. DATA SYNTHESIS: Key points pertaining to PPAR function and involvement in colon pathology were extracted and noted. Potential compromises to therapeutic utility are identified. CONCLUSIONS: The emerging important role of PPAR gamma in normal tissue homeostasis and pathologic outcomes suggests this receptor is a good candidate as a drug target. Several potential problems with this approach will require further investigation prior to widespread recommendations for modulation of PPAR as an efficacious therapy for cancer, chemoprevention of colon cancer, or treatment of inflammatory bowel disease. The widespread use of PPAR gamma ligands for management of type 2 diabetes (such as the glitazone class of drugs including rosiglitazone and pioglitazone) may provide a fortuitous assessment of the efficacy of long-term PPAR modulation.
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