Effects of a New PPARgamma Agonist on Tongue Carcinoma Cells

Abstract

Objective: To investigate the effects of GW1929, a new specific PPARgamma agonist, on head and neck squamous carcinoma cell proliferation, apoptosis, and invasion.

Method: Human well-differentiated tongue SCC15 cells were treated with 5, 10, 20 micromolar GW1929, and 1% DMSO in 2% FBS Media (control). Tetrazolilum salt WST-1 assay was used to assess proliferation. Cell cycle was analyzed with FACS. Caspase3 was measured with Caspase-Glo3/7 luminescent. RT-PCR measured metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 mRNA to assess anti-invasive effects.

Results: GW1929 inhibited tumor cell proliferation. At 24, 48, and 72 hours, treatment with 5, 10, and 20 micromolar GW1929 inhibited SCC15 proliferation by 12% to 23%, 17% to 31%, 27% to 45% in a dose-dependent manner. FACS analysis showed that GW1929 prevented cells from entering S-phase of cell cycle. Confirming significant cellular apoptosis, levels of caspase 3 were 154%, 163%, 185% of control after a 24-hour treatment with 5, 10, 20 micromolar GW1929. GW1929 decreased expression of markers of extracellular matrix invasion in a dose-dependent manner. At 24 hours, levels of MMP-9 mRNA were decreased up to 2 fold, and levels of TIMP-1 mRNA were increased up to 2 fold.

Conclusion: GW1929 is a potential antiproliferative agent, as evidenced by its pro-apoptotic, anti-proliferative, and anti-invasive effect on squamous carcinoma of the tongue.