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

Yih Ho, Chien Yi Wu, Yu Tang Chin, Zi Lin Li, Yi shin Pan, Tung Yung Huang, Po Yu Su, Sheng Yang Lee, Dana R. Crawford, Kuan Wei Su, Hsien Chung Chiu, Ya Jung Shih, Chun A. Changou, Yu Chen S.H. Yang, Jaqulene Whang-Peng, Yi Ru Chen, Hung Yun Lin, Shaker A. Mousa, Paul J. Davis, Kuan Wang

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4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number111092
Pages (from-to)111092
JournalFood and Chemical Toxicology
Volume136
DOIs
Publication statusPublished - Feb 1 2020

Keywords

  • L-thyroxine
  • NDAT
  • Oral cancer
  • Programmed death ligand 1
  • Resveratrol

ASJC Scopus subject areas

  • Food Science
  • Toxicology

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  • Cite this

    Ho, Y., Wu, C. Y., Chin, Y. T., Li, Z. L., Pan, Y. S., Huang, T. Y., Su, P. Y., Lee, S. Y., Crawford, D. R., Su, K. W., Chiu, H. C., Shih, Y. J., Changou, C. A., Yang, Y. C. S. H., Whang-Peng, J., Chen, Y. R., Lin, H. Y., Mousa, S. A., Davis, P. J., & Wang, K. (2020). NDAT suppresses pro-inflammatory gene expression to enhance resveratrol-induced anti-proliferation in oral cancer cells. Food and Chemical Toxicology, 136, 111092. [111092]. https://doi.org/10.1016/j.fct.2019.111092