PPARγ-Mediated p21 Induction in Aerodigestive Preneoplastic Cell Lines

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Oral leukoplakia presents as white patches, is the most common potentially premalignant oral disorder, and is a candidate for chemoprevention.
• Pioglitazone activates peroxisome proliferator-activated receptor gamma (PPARγ), influencing cell-cycle gene expression and is under investigation for aerodigestive cancer prevention.

Purpose of the Study:

• To investigate if pioglitazone decreases proliferation in human leukoplakia (MSK Leuk1) and bronchial epithelial (BEAS-2B) cells.
• To determine if pioglitazone affects G1 checkpoint protein regulators, specifically p21 and cyclin-D1.

Main Methods:

• MSK Leuk1 and BEAS-2B cells were treated with varying doses of pioglitazone.
• Cell proliferation was measured.
• p21 transcriptional activity and protein levels were assessed.

Main Results:

• Pioglitazone significantly inhibited cell proliferation in a dose-dependent manner.
• Treatment with pioglitazone induced p21 protein.
• Increased p21 mRNA levels preceded p21 protein induction.

Conclusions:

• Pioglitazone, a PPARγ activator, decreases proliferation in aerodigestive preneoplastic cell lines by activating p21.
• The p21 gene shows potential as a biomarker for pioglitazone's chemopreventive effects in aerodigestive cancers.