Abstract 601: PPARδ mediated p21 induction in aerodigestive preneoplastic cell lines

Abstract

Abstract PPARδ activating strategies are currently being tested preclinically and clinically in aerodigestive cancer prevention. Thiazolidinedione drugs like pioglitazone are clinically used for the treatment of diabetes and activate PPARδ as a primary target. P21/WAF1 is a cell cycle protein that is a cyclin dependent kinase inhibitor that reguylates cell cycle progression at the G1 phase; therefore its induction may be associated with cell cycle downregulation in precancerous cells experiencing increased proliferation. In our present study we examined the effects of pioglitazone on proliferation in human leukoplakia cells (MSK 1) and transformed lung (BEAS 2B) cells. We found that pioglitazone significantly inhibited cell proliferation in both cell lines in a dose dependent fashion at concentrations between 0 and 40 uM, as judged by MTT assays from 1-5 days. We found p21/WAF 1 induction by western blot within the first eight hours after the intitiation of treatment with pioglitazone, which were preceded by measureable increases in p21 induction on q PCR. In an analysis of an Affymetrix database of human head and neck tumors (41 tumors compared to 13 normal oral mucosa samples), we found significant dysregulation in several p21 activated kinases. We conclude the PPARδ activator, pioglitazone, can activate p21, which is associated with decreased proliferation in 2 aerodigestive preneoplastic cell lines. We also conclude that this gene may be a potential hypothesis driven biomarker in translational studies of pioglitazone as a chemoprevention agent for aerodigestive cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 601. doi:1538-7445.AM2012-601