RESUMO
OBJECTIVE: The effect of thyroid hormone (TH) on cancers was proposed more than 100 years ago; however, conclusions are conflicting. THs are precisely regulated at tissue and cellular levels. It seems that this regulation is altered in cancers. Thyroid hormone receptor beta (TRß) has anti-proliferative and tumor-suppressive effects in many cancer cells. Therefore, we decided to investigate thyroid hormone receptor beta (THRB) expression and activation by the selective agonist, GC-1, on tumor growth in a syngeneic mouse model of colorectal cancer (CRC) and colon cell lines. METHODS: In vitro cell viability assay using MTT analysis, cell cycle analysis by PI staining, and FACS analysis were performed. In vivo tumor growth measurements were carried out by caliper and [18F] Fluoro-2-deoxy-2-D-glucose (FDG) - PET imaging. Gene expressions were determined using quantitative-PCR. RESULTS: Some concentrations of GC-1 had a marked negative effect on the cell viability of colorectal cell lines. Cell cycle analysis showed that the anti-proliferative effect of GC-1 may not result from cell cycle arrest or apoptosis. Tumor growth analysis in mice harboring colorectal tumor showed that GC-1 treatment for 8 d profoundly inhibited tumor growth and 18FDG uptake. THRB expression was decreased in mice tumor; however, it was upregulated following GC-1 administration. CONCLUSIONS: Our results showed that specific activation of TRß by GC-1 had negative effect on tumor growth and restored its gene expression in tumors of CRC mice model.
Assuntos
Neoplasias Colorretais , Receptores beta dos Hormônios Tireóideos , Acetatos , Animais , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Modelos Animais de Doenças , Fluordesoxiglucose F18 , Glucose , Camundongos , Fenóis , Receptores beta dos Hormônios Tireóideos/genética , Receptores beta dos Hormônios Tireóideos/metabolismo , Hormônios TireóideosRESUMO
This research was financially supported by National Institute for Medical Research Development (NIMAD).
RESUMO
This study was designed to investigate the brain toxicity following the respiratory contact with multi-wall carbon nanotubes (MWCNTs) in male Wistar rats. Rats were exposed to 5 mg/m3 MWCNT aerosol in different sizes and purities for 5 h/day, 5 days/week for 2 weeks in a whole-body exposure chamber. After 2-week exposure, mitochondrial isolation was performed from different parts of rat brain (hippocampus, frontal cortex, and cerebellum) and parameters of mitochondrial toxicity including mitochondrial succinate dehydrogenase (SDH) activity, generation of reactive oxygen species (ROS), mitochondrial membrane potential (MMP) collapse, mitochondrial swelling, and cytochrome c release, ATP level, mitochondrial GSH, and lipid peroxidation were evaluated. Our results demonstrated that MWCNTs with different characteristics, in size and purity, significantly (P < 0.05) decreased SDH activity, GSH, and ATP level, and increased mitochondrial ROS production, lipid peroxidation, mitochondrial swelling, MMP collapse, and cytochrome c release in the brain mitochondria. In conclusion, we suggested that MWCNTs with different characteristics, in size and purity, induce damage in varying degrees on the mitochondrial respiratory chain and increase mitochondrial ROS formation in different parts of rat brain (hippocampus, frontal cortex, and cerebellum).