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In vitro: Troglitazone significantly inhibits cell growth by cell cycle arrest and apoptotic cell death. Troglitazone also downregulates surface expression of CD97, a novel dedifferentiation marker, in FTC-133 cells and upregulated sodium iodide symporter (NIS) mRNA in TPC-1 and FTC-133 cells. Troglitazone, a PPARγ agonist, induces antiproliferation and redifferentiation in thyroid cancer cell lines. Troglitazone induces Erk phosphorylation in human prostate cancer cells via a PPARγ-independent signaling pathway. TGZ(Troglitazone) up-regulates nitric oxide synthesis, induces the p53 pathway, inhibits cholesterol biosynthesis, induces p21 cyclin-dependent kinase inhibitor, has antioxidant function, and activates extracellular signal-regulated protein kinase (ERK) in a PPARγ-independent manner. TGZ induces Egr-1 expression by transcriptional and post-transcriptional regulation. Egr-1 induction by TGZ results in the increase of binding affinity and transactivation of the promoter containing Egr-1 consensus sequences, thereby possibly inducing other anti-tumorigenic proteins. In vivo: Troglitazone is an effective antidiabetic drug with a fundamentally new mechanism of action. However, within a year after its widespread use, individual cases of liver injury and failure are reported. TGZ significantly inhibits tumor growth of human colorectal cancer cells (HCT-116), human breast cancer cells (MCF-7), and human prostate cancer cells (PC-3) in immunodeficient mice. Troglitazone attenuates pancreatic damage and inflammation in experimental chronic pancreatitis.
| Cell Experiment | |
|---|---|
| Cell lines | Thyroid cancer cell lines TPC-1, FTC-133, FTC-236, FTC-238, XTC-1 and ARO82-1 cell lines |
| Preparation method | Growth experiments are done in a 96-well plate in hexaplicate. Cells at 85%-100% confluency are harvested with 1×Trypsin/EDTA solution and seeded into a 96-well plate at 3-5×103 cells per well depending upon growth rate and maintained in 200 μL H5 medium in a humidified incubator. After 24 hours, cells are incubated with different concentrations of troglitazone and the media was changed daily. Colorometric dimethyl-thiazol-diphenyltetrazolium bromide (MTT) proliferation assays are performed at 0, 2, 4, and 6 days after treatment. MTT (400 μg/mL) is added to each well and incubated for 3 hours. It is solubilized with 0.04 N HCl/iso-propanol/3% SDS and incubated for 1 hour. The optical densities in the 96-well plates are determined using an enzyme-linked immunosorbent assay (ELISA) microplate reader at 595 nm/620 nm. |
| Concentrations | 5, 10, 20, 40 μM |
| Incubation time | 0, 2, 4, and 6 days |
| Animal Experiment | |
|---|---|
| Animal models | C57BL/6 mice |
| Formulation | |
| Dosages | 0.2% (with chow) |
| Administration | oral administration |
| Molecular Weight | 441.54 |
| Formula | C24H27NO5S |
| CAS Number | 97322-87-7 |
| Solubility (25°C) | DMSO ≥ 60 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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