Retinoids Augment Thiazolidinedione PPARγ Activation in Oral Cancer Cells

  • Anticancer Res. 2020 Jun;40(6):3071-3080. doi: 10.21873/anticanres.14288.
Raul Rosas  1 ,  Seth Buryska  2 ,  Robert Silver  3 ,  Beverly Wuertz  4 ,  Frank Ondrey  2
Affiliations
  • 1. Ear, Nose, & Throat Surgery, Essentia Health, Duluth, MN, U.S.A.
  • 2. Department of Otolaryngology-Head and Neck Surgery, University of Minnesota, Minneapolis, MN, U.S.A.
  • 3. Ear, Nose & Throat Specialty Care, Minneapolis, MN, U.S.A.
  • 4. Department of Otolaryngology-Head and Neck Surgery, University of Minnesota, Minneapolis, MN, U.S.A. [email protected].
PMID: 32487601 DOI: 10.21873/anticanres.14288
Abstract

Background/aim: Head and neck squamous cell carcinoma affects nearly 500,000 people annually. Augmenting PPARγ functional activation is linked with multiple anti-carcinogenic processes in aerodigestive cell lines and animal models. PPARγ/RXRα heterodimers may be key partners in this activation.

Materials and methods: CA 9-22 and NA cell lines were treated with the PPARγ Agonist ciglitazone and/or the RXRα Agonist 9-cis-retinoic acid. PPARγ functional activation, cellular proliferation, Apoptosis activity, and phenotype were subsequently analyzed.

Results: Ciglitazone and 9-cis-retinoic acid independently activated PPARγ and down-regulated the carcinogenic phenotype in vitro. Combination treatment significantly augmented these effects, further decreasing proliferation (p<0.0001), and increasing PPARγ 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.

Keywords
9-cis-retinoic acid; PPARγ; ciglitazone; head and neck squamous carcinoma; retinoids; thiazolidinedione.
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