NDAT suppresses pro-inflammatory gene expression to enhance resveratrol-induced anti-proliferation in oral cancer cells

Food Chem Toxicol. 2020 Feb:136:111092. doi: 10.1016/j.fct.2019.111092. Epub 2019 Dec 26.


Nano-diamino-tetrac (NDAT), a tetraiodothyroxine deaminated nano-particulated analog, has shown to inhibit expression of pro-inflammatory genes. NDAT inhibits expression of programmed death-ligand 1 (PD-L1). On the other hand, in addition to inhibiting inflammatory effect, the stilbene, resveratrol induces expression of cyclooxygenase-2 (COX-2) and its accumulation. Sequentially, inducible COX-2 complexes with p53 and induces p53-dependent anti-proliferation. In current study, we investigated mechanisms involved in combined treatment of NDAT and resveratrol on anti-proliferation in human oral cancer cells. Both resveratrol and NDAT inhibited expression of pro-inflammatory IL-1β and TNF-α. They also inhibited expression of CCND1 and PD-L1. Both resveratrol and NDAT induced BAD expression but only resveratrol induced COX-2 expression in both OEC-M1 and SCC-25 cells. Combined treatment attenuated gene expression significantly compared with resveratrol treatment in both cancer cell lines. Resveratrol reduced nuclear PD-L1 accumulation which was enhanced by a STAT3 inhibitor, S31-201 or NDAT suggesting that NDAT may inactivate STAT3 to inhibit PD-L1 accumulation. In the presence of T4, NDAT further enhanced resveratrol-induced anti-proliferation in both cancer cell lines. These findings provide a novel understanding of the inhibition of NDAT in thyroxine-induced pro-inflammatory effect on resveratrol-induced anticancer properties.

Keywords: L-thyroxine; NDAT; Oral cancer; Programmed death ligand 1; Resveratrol.

MeSH terms

  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / immunology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / immunology
  • Drug Synergism
  • Gene Expression
  • Humans
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / immunology
  • Mouth Neoplasms / physiopathology*
  • Polyglactin 910 / pharmacology*
  • Resveratrol / pharmacology*
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / immunology
  • Thyroxine / analogs & derivatives*
  • Thyroxine / pharmacology


  • B7-H1 Antigen
  • CCND1 protein, human
  • CD274 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • nano-diamino-tetrac
  • Cyclin D1
  • Polyglactin 910
  • Cyclooxygenase 2
  • Resveratrol
  • Thyroxine