title: Nuclear receptor agonists as potential differentiation therapy agents for human osteosarcoma.
abstract: OBJECTIVE
  This study was designed to investigate whether nuclear receptor agonists can be used as potential differentiation therapy agents for human osteosarcoma.
  
  
  METHODS
  Four osteosarcoma cell lines (143B, MNNG/HOS, MG-63, and TE-85) were treated with proliferator-activated receptor (PPAR)gamma 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 PPARgamma was readily detected in all tested osteosarcoma lines. On treatment with the PPARgamma 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 PPARgamma 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.
authors: Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Illinois 60637, USA.
authors: Rex C
authors: RC
authors: Haydon
authors: Lan
authors: L
authors: Zhou
authors: Tao
authors: T
authors: Feng
authors: Benjamin
authors: B
authors: Breyer
authors: Hongwei
authors: H
authors: Cheng
authors: Wei
authors: W
authors: Jiang
authors: Akira
authors: A
authors: Ishikawa
authors: Terrance
authors: T
authors: Peabody
authors: Anthony
authors: A
authors: Montag
authors: Michael A
authors: MA
authors: Simon
authors: Tong-Chuan
authors: TC
authors: He
mesh_terms: D000077556:Alitretinoin; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000819:agonists; D047488:Retinoid X Receptors; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D013997:Time Factors; D014157:Transcription Factors / Q000819:agonists / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology*; D000077288:Troglitazone; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002839:Chromans; D012334:RNA, Neoplasm; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077556:Alitretinoin; D014212:Tretinoin; D000077288:Troglitazone; C039671:ciglitazone