Effects of PPAR-γ agonists on oral cancer cell lines: Potential horizons for chemopreventives and adjunctive therapies

Head Neck. 2020 Sep;42(9):2542-2554. doi: 10.1002/hed.26286. Epub 2020 Jun 9.

Abstract

Background: Peroxisome proliferator-activated receptor-gamma (PPAR-γ) activators have anti-cancer effects. Our objective was to determine the effect of PPAR-γ ligands 15-deoxy-D12,14 -Prostaglandin J2 (15-PGJ2 ) and ciglitazone on proliferation, apoptosis, and NF-κB in human oral squamous cell carcinoma cell lines.

Methods: NA and CA9-22 cells were treated in vitro with 15-PGJ2 and ciglitazone. Proliferation was measured by MTT colorimetric assay and cell cycle analysis performed via flow cytometry, apoptosis by caspase-3 colorimetric assay and poly-(ADP-ribose) polymerase cleavage on Western blot, and NF-κB activation by luciferase assays.

Results: MTT assays demonstrated dose-dependent decreases after 15-PGJ2 treatment in both cell lines, and S-phase cell cycle arrest was also demonstrated. NF-κB luciferase reporter gene activity decreased seven- and eightfold in NA and CA9-22 cells, respectively. Caspase-3 activity increased two- and eightfold in NA and CA9-22 cells, respectively.

Conclusions: Our results suggest these agents, in addition to activating PPAR-γ, can downregulate NF-κB and potentiate apoptosis in oral cancer cells.

Keywords: 15-deoxy-D12,14-prostaglandin J2 (15-PGJ2); Ciglitazone; NF-κB; PPAR-γ; squamous cell carcinoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell* / drug therapy
  • Cell Line
  • Humans
  • Mouth Neoplasms* / drug therapy
  • PPAR gamma
  • Prostaglandin D2

Substances

  • PPAR gamma
  • Prostaglandin D2