PPAR-gamma Inhibitors: Potential Anti-Cancer Compounds

Filed in archive Drugs, Vaccines and Therapeutics on February 5, 2007

Scientists have identified a group of compounds called peroxisome proliferator-activated receptor-gamma (PPARγ) inhibitors which may help treat colorectal cancer, and potentially cancers of the esophagus, liver and skin. However, the anti-cancer effect does not appear to be linked to the ability of the compounds to inhibit PPARγ function; researchers believe that PPARγ inhibitors instead reducing levels of the proteins called tubulins, the building blocks of cancer cell skeletons that enable them to reproduce, grow and spread.

In the newly published study, researchers observed the effects of three compounds known from the literature to inhibit PPARγ, T0070907, GW9662 and BADGE, on the ability of colorectal tumor cells to survive. High doses (10-100 μM) of all three interfered with colorectal cancer cell growth, reduced the cells' ability to spread through the bloodstream to cause new tumors elsewhere (metastasize) and caused cells to self-destruct, generally within 24 hours. Further experiments showed that high-dose PPARγ inhibition destroyed cancer cell microtubules, protein structures that form part of the skeleton of cells.

This reasearch has been published in the journal International Cancer Research. For an overview, see the University of Rochester press release.

The research team will next seek to determine exactly which proteins are involved in the anti-cancer effect of PPARγ inhibitors.

[Image: Wikipedia]