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)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.
PURPOSE: This study was designed to investigate whether nuclear receptor agonists can be used as potential differentiation therapy agents for humanosteosarcoma. EXPERIMENTAL DESIGN: 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: S Minucci; M Maccarana; M Cioce; P De Luca; V Gelmetti; S Segalla; L Di Croce; S Giavara; C Matteucci; A Gobbi; A Bianchini; E Colombo; I Schiavoni; G Badaracco; X Hu; M A Lazar; N Landsberger; C Nervi; P G Pelicci Journal: Mol Cell Date: 2000-05 Impact factor: 17.970
Authors: G D Demetri; C D Fletcher; E Mueller; P Sarraf; R Naujoks; N Campbell; B M Spiegelman; S Singer Journal: Proc Natl Acad Sci U S A Date: 1999-03-30 Impact factor: 11.205
Authors: Gaurav Luther; Richard Rames; Eric R Wagner; Gaohui Zhu; Qing Luo; Yang Bi; Stephanie H Kim; Jian-Li Gao; Enyi Huang; Ke Yang; Linyuan Wang; Xing Liu; Mi Li; Ning Hu; Yuxi Su; Xiaoji Luo; Liang Chen; Jinyong Luo; Rex C Haydon; Hue H Luu; Lan Zhou; Tong-Chuan He Journal: Trends Cancer Res Date: 2010
Authors: Xiaojun Wang; Jing Cui; Bing-Qiang Zhang; Hongyu Zhang; Yang Bi; Quan Kang; Ning Wang; Ping Bie; Zhanyu Yang; Huaizhi Wang; Xiangde Liu; Rex C Haydon; Hue H Luu; Ni Tang; Jiahong Dong; Tong-Chuan He Journal: J Biomed Mater Res A Date: 2013-06-04 Impact factor: 4.396