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Correlative Studies Unravelling the Possible Mechanism of Cell Death in Tideglusib-Treated Human Ovarian Teratocarcinoma-Derived PA-1 Cells.
- Source :
-
Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer [J Environ Pathol Toxicol Oncol] 2017; Vol. 36 (4), pp. 321-344. - Publication Year :
- 2017
-
Abstract
- This study aims to unravel the use of GSK-3 inhibitors as viable apoptotic inducers for teratocarcinoma-derived ovarian PA-1 cells. MTT assay was carried out to assess inhibitory concentrations of LiCl and TDG. AO/EB staining and Hoechst 33258 staining were employed to assess the damage. Mitochondrial membrane potential (ΔΨm) and ROS generation were assessed with IC50 concentrations of LiCl and TDG. Tumor-related genes (p53, p21, IL-8, TNF-α, MMP-2, Fas-L, Cox-2, and caspase-3) were assessed with 1/4 IC50, 1/2 IC50, IC50 concentrations by semi-quantitative RT- PCR. Cell cycle analysis was performed with IC50 concentration of LiCl and TDG. Western blot analysis was performed for caspase-3, caspase-7, caspase-9, PARP to estimate the possible damage induced by GSK-3 inhibitors and regulation of GSK-3β, pGSK-3β, Cox-2. GSK-3 inhibitors demonstrated a concentration and time-dependent reduction in cell viability, exhibiting significant ROS generation and reduced ΔΨm at their IC50 values. Substantial concentration-dependent gene expression changes with significant upregulation of P21, Cox-2, TNF-α, caspase-3, Fas-L were observed. Protein expression of caspase-3 caspase-7, caspase-9, PARP exhibited significant cleavage in LiCl and TDG-treated cells. Protein expression of Cox-2 was significantly increased in IC50 concentration of TDG. Cell cycle analysis showed significant accumulation of cells at sub-G0-G1.
- Subjects :
- Cell Line, Tumor
Cyclin-Dependent Kinase Inhibitor p21 genetics
Dose-Response Relationship, Drug
Female
Humans
Lithium Chloride pharmacology
Matrix Metalloproteinase 2 genetics
Membrane Potential, Mitochondrial
Ovarian Neoplasms pathology
Reactive Oxygen Species metabolism
Teratocarcinoma pathology
Apoptosis drug effects
Glycogen Synthase Kinase 3 antagonists & inhibitors
Ovarian Neoplasms drug therapy
Teratocarcinoma drug therapy
Thiadiazoles pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2162-6537
- Volume :
- 36
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 29431064
- Full Text :
- https://doi.org/10.1615/JEnvironPatholToxicolOncol.2017025018