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PPAR Research
Volume 2008, Article ID 785405, 9 pages
http://dx.doi.org/10.1155/2008/785405
Review Article

PPAR Inhibitors as Novel Tubulin-Targeting Agents

Gastroenterology and Hepatology Division, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA

Received 29 February 2008; Accepted 1 May 2008

Academic Editor: Dipak Panigrahy

Copyright © 2008 Katherine L. Schaefer. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The microtubule-targeting agents (MTAs) are a very successful class of cancer drugs with therapeutic benefits in both hematopoietic and solid tumors. However, resistance to these drugs is a significant problem. Current MTAs bind to microtubules, and/or to their constituent tubulin heterodimers, and affect microtubule polymerization and dynamics. The PPAR inhibitor T0070907 can reduce tubulin levels in colorectal cancer cell lines and suppress tumor growth in a murine xenograft model. T0070907 does not alter microtubule polymerization in vitro, and does not appear to work by triggering modulation of tubulin RNA levels subsequent to decreased polymerization. This observation suggests the possible development of antimicrotubule drugs that work by a novel mechanism, and implies the presence of cancer therapeutic targets that have not yet been exploited. This review summarizes what is known about PPAR inhibitors and cancer cell death, with emphasis on the tubulin phenotype and PPAR-dependence, and identifies potential mechanisms of action.