Inhibition of tumorigenesis by peroxisome proliferator-activated receptor (PPAR)-dependent cell cycle blocks in human skin carcinoma cells.

Autor: Borland MG; Department of Veterinary and Biomedical Sciences, The Center of Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA 16802, USA; Department of Chemistry & Biochemistry, Bloomsburg University of Pennsylvania, Bloomsburg, PA 17815, USA., Kehres EM; Department of Chemistry & Biochemistry, Bloomsburg University of Pennsylvania, Bloomsburg, PA 17815, USA., Lee C; Department of Veterinary and Biomedical Sciences, The Center of Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA 16802, USA., Wagner AL; Department of Chemistry & Biochemistry, Bloomsburg University of Pennsylvania, Bloomsburg, PA 17815, USA., Shannon BE; Department of Chemistry & Biochemistry, Bloomsburg University of Pennsylvania, Bloomsburg, PA 17815, USA., Albrecht PP; Department of Veterinary and Biomedical Sciences, The Center of Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA 16802, USA., Zhu B; Department of Veterinary and Biomedical Sciences, The Center of Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA 16802, USA., Gonzalez FJ; Laboratory of Metabolism, National Cancer Institute, Bethesda, MD 20892, USA., Peters JM; Department of Veterinary and Biomedical Sciences, The Center of Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA 16802, USA. Electronic address: jmp21@psu.edu.
Jazyk: angličtina
Zdroj: Toxicology [Toxicology] 2018 Jul 01; Vol. 404-405, pp. 25-32. Date of Electronic Publication: 2018 May 03.
DOI: 10.1016/j.tox.2018.05.003
Abstrakt: To examine the functional role of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) and PPARγ in skin cancer, stable cell lines were created in the A431 human squamous cell carcinoma cell line. Expression of PPAR target genes was greatly enhanced in response to ligand activation of PPARβ/δ or PPARγ in A431 cells expressing these receptors. PPARβ/δ expression blocked the cell cycle at the G2/M phase, and this effect was increased by ligand activation. Ligand activation of PPARβ/δ markedly inhibited clonogenicity as compared to vehicle-treated controls. Similarly, ligand activation of PPARγ in A431 cells expressing PPARγ resulted in reduced clonogenicity. Expression of either PPARβ/δ or PPARγ markedly reduced tumor volume in ectopic xenografts, while ligand activation of these receptors had little further influence on tumor volume. Collectively, these studies demonstrate that stable expression and activation of PPARβ/δ or PPARγ in A431 cells led to reduced tumorigenicity. Importantly, PPAR expression or ligand activation had major impacts on clonogenicity and/or tumor volume. Thus, PPARβ/δ or PPARγ could be therapeutically targeted for the treatment of squamous cell carcinomas.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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