Nuclear receptor agonists as potential differentiation therapy agents for human osteosarcoma

Rex C. Haydon, Lan Zhou, Tao Feng, Benjamin Breyer, Hongwei Cheng, Wei Jiang, Akira Ishikawa, Terrance Peabody, Anthony Montag, Michael A. Simon, Tong Chuan He*

*Corresponding author for this work

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

Purpose: This study was designed to investigate whether nuclear receptor agonists can be used as potential differentiation therapy agents for human osteosarcoma. Experimental Design: Four osteosarcoma cell lines (143B, MNNG/HOS, MG-63, and TE-85) were treated with proliferator-activated receptor (PPAR)γ agonists, troglitazone and ciglitazone, and a retinoid X receptor (RXR) ligand, 9-cis retinoic acid. The proliferation and induction of apoptosis in the treated cells were assessed, as was the induction of alkaline phosphatase, a differentiation marker of osteoblasts. Results: The expression of PPARγ was readily detected in all tested osteosarcoma lines. On treatment with the PPARγ and RXR ligands, all four osteosarcoma lines exhibited a significantly reduced proliferation rate and cell viability. Among the four lines, 143B and MNNG/HOS were shown to be more sensitive to ligand-induced apoptosis, as demonstrated by the Crystal Violet and Hoechst staining assays. Of the three tested ligands, troglitazone was shown to be the most effective in inducing cell death, followed by 9-cis retinoic acid. Moreover, a strong synergistic effect on the induction of cell death was observed when both troglitazone and 9-cis retinoic acid or ciglitazone and 9-cis retinoic acid were administered to osteosarcoma cells. Troglitazone was shown to effectively induce alkaline phosphatase activity, a well-characterized hallmark for osteoblastic differentiation. Conclusions: Our findings suggest that PPARγ and/or RXR ligands may be used as efficacious adjuvant therapeutic agents for primary osteosarcoma, as well as potential chemopreventive agents for preventing the recurrence and metastasis of osteosarcoma after the surgical removal of the primary tumors.

Original languageEnglish (US)
Pages (from-to)1288-1294
Number of pages7
JournalClinical Cancer Research
Volume8
Issue number5
StatePublished - May 27 2002

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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