Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin increases the activation of aryl hydrocarbon receptor and is associated with the aggressiveness of osteosarcoma MG-63 osteoblast-like cells

Shih Chieh Yang, Chin Hsien Wu, Yuan Kun Tu, Shin Yu Huang, Pai Chien Chou

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The aryl hydrocarbon receptor (AhR) is a liganddependent transcription factor whose activity is modulated by xenobiotics and physiological ligands. Activation of the AhR by environmental xenobiotics may induce a conformational change in AhR and has been implicated in a variety of cellular processes, including inflammation and tumorigenesis. It is unknown whether the activation of AhR serves a role in modulating the progression of osteosarcoma. The osteosarcoma cell line MG-63, was treated with AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD treatment degrades AhR expression through activation of the AhR signaling pathway, however there were no survival differences observed in MG-63 cells. There were concomitant elevations of cyclooxygenase-2 and receptor activator of nuclear factor-κB ligand secretion from MG-63 cells upon TCDD treatment on a protein and mRNA level at 24 and 72 h. In addition, TCDD treatment also increases the production of prostaglandin E2 on MG-63 cells, and induces the expression of chemokine receptor CXCR4. However, CXCL12 production was not altered in MG-63 cells when stimulated with TCDD. The AhR antagonist CH-223191, blocks the effects on TCDD-induced RANKL, COX-2, PGE2 and CXCR4 changes. In conclusion, these findings suggest that AhR signal therapy should be further explored as a therapeutic option for the treatment of osteosarcoma.

Original languageEnglish
Pages (from-to)3849-3857
Number of pages9
JournalOncology Letters
Volume16
Issue number3
DOIs
Publication statusPublished - Sep 1 2018
Externally publishedYes

Keywords

  • 2,3,7,8-tetrachlorodibenzo-p-dioxin
  • Aryl hydrocarbon receptor
  • Osteoblast
  • Osteosarcoma
  • Receptor activator of nuclear factor κΒ ligand

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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