PURPOSE: The peroxisome proliferator-activated receptor gamma (PPARγ), a member of the nuclear hormone receptor family, represents a target in glioma therapy due to its antineoplastic effects in vitro on human glioma cell lines. We investigate the antineoplastic effects of the PPARγ agonist pioglitazone (pio) in a human glioma xenograft model to define the minimal required dose to induce antineoplastic effects. Additionally, we assess the ability of pio to cross the blood-brain barrier by measuring brain parenchymal concentration after oral administration. METHODS: Human LN-229 cells were injected into the striatum of Balb/cJHanHsd-Prkdc-scid mice. Tumor volumes, invasion, proliferation and parenchymal pio concentrations were measured in this xenograft model after continuous intracerebral drug administration through an osmotic pump or after oral administration. RESULTS: Continuous intracerebral or oral administration of pio reduced tumor volumes, invasion, and proliferation in vivo. To achieve a significant antineoplastic effect, pio needed to be dosed at 240 PPM in the oral group and >1 μM when delivered intracerebrally. After oral pio administration, the drug reached >1 nM levels in brain parenchyma. CONCLUSIONS: These data indicate that pioglitazone crosses the blood-brain barrier and has antineoplastic effects in this glioma xenograft model and may be of potential use in treatment of malignant gliomas.
PURPOSE: The peroxisome proliferator-activated receptor gamma (PPARγ), a member of the nuclear hormone receptor family, represents a target in glioma therapy due to its antineoplastic effects in vitro on humanglioma cell lines. We investigate the antineoplastic effects of the PPARγ agonist pioglitazone (pio) in a humanglioma xenograft model to define the minimal required dose to induce antineoplastic effects. Additionally, we assess the ability of pio to cross the blood-brain barrier by measuring brain parenchymal concentration after oral administration. METHODS:Human LN-229 cells were injected into the striatum of Balb/cJHanHsd-Prkdc-scid mice. Tumor volumes, invasion, proliferation and parenchymal pio concentrations were measured in this xenograft model after continuous intracerebral drug administration through an osmotic pump or after oral administration. RESULTS:Continuous intracerebral or oral administration of pio reduced tumor volumes, invasion, and proliferation in vivo. To achieve a significant antineoplastic effect, pio needed to be dosed at 240 PPM in the oral group and >1 μM when delivered intracerebrally. After oral pio administration, the drug reached >1 nM levels in brain parenchyma. CONCLUSIONS: These data indicate that pioglitazone crosses the blood-brain barrier and has antineoplastic effects in this glioma xenograft model and may be of potential use in treatment of malignant gliomas.
Authors: Christina K Cramer; Natalie Alphonse-Sullivan; Scott Isom; Linda J Metheny-Barlow; Tiffany L Cummings; Brandi R Page; Doris R Brown; Arthur W Blackstock; Ann M Peiffer; Roy E Strowd; Stephen Rapp; Glenn J Lesser; Edward G Shaw; Michael D Chan Journal: J Cancer Res Clin Oncol Date: 2018-11-12 Impact factor: 4.553
Authors: Alana de Vasconcelos; Larissa Ribeiro de Moura; Nathalia Stark Pedra; Natália Pontes Bona; Mayara Sandrielly Pereira Soares; Magno da Silva Marques; Ana Paula Horn; Luiza Spohr; Roselia Maria Spanevello; Francieli Moro Stefanello; Wilson Cunico Journal: Metab Brain Dis Date: 2022-05-26 Impact factor: 3.655