2020 Anticancer research

Retinoids Augment Thiazolidinedione PPARgamma Activation in Oral Cancer Cells.

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Anticancer research Vol. 40 (6) : 3071-3080 • Jun 2020

BACKGROUND/AIM: Head and neck squamous cell carcinoma affects nearly 500,000 people annually. Augmenting PPARgamma functional activation is linked with multiple anti-carcinogenic processes in aerodigestive cell lines and animal models. PPARgamma/RXRalpha heterodimers may be key partners in this activation. MATERIALS AND METHODS: CA 9-22 and NA cell lines were treated with the PPARgamma agonist ciglitazone and/or the RXRalpha agonist 9-cis-retinoic acid. PPARgamma functional activation, cellular proliferation, apoptosis activity, and phenotype were subsequently analyzed. RESULTS: Ciglitazone and 9-cis-retinoic acid independently activated PPARgamma and down-regulated the carcinogenic phenotype in vitro. Combination treatment significantly augmented these effects, further decreasing proliferation (p<0.0001), and increasing PPARgamma functional activation (p<0.0001), apoptosis (p<0.05), and adipocyte differentiation markers (p<0.0001). CONCLUSION: The efficacy of the combination of ciglitazone and 9-cis-retinoic acid afforded lowering treatment concentrations while maintaining desired therapeutic outcomes, optimistically supporting the feasibility and practicality of this novel treatment option.

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