AI Article Synopsis
- The study explores the potential of 7 Methyl-indole ethyl isothiocyanate (7Me-IEITC) as a treatment for advanced endometrial cancer, highlighting the need for new therapies.
- 7Me-IEITC was found to significantly reduce the viability of endometrial cancer cell lines (ECC-1 and KLE) through mechanisms involving apoptosis and mitochondrial dysfunction.
- The compound's effect was linked to oxidative stress and specific changes in protein expression, indicating its cytotoxicity may be primarily due to ROS production, suggesting further research is warranted.
Article Abstract
Objective: Chemotherapy options for advanced endometrial cancer are limited and newer therapeutic agents are urgently needed. This study describes the therapeutic potential of 7 Methyl-indole ethyl isothiocyanate (7Me-IEITC) in endometrial cancer cell lines.
Methods: 7Me-IEITC was synthesized in our laboratory. The cell viability of 7Me-IEITC treated ECC-1 and KLE endometrial cancer cell was determined by MTS assay. Morphology and apoptosis were further confirmed by DAPI-staining and TUNEL assay. The measurement of reactive oxygen species (ROS), mitochondrial transmembrane depolarization potential (ΔΨm) and cell cycle phase was determined by FACS analysis. Expression of proteins involved in apoptosis, survival and cell-cycle progression was analyzed by Western blotting.
Results: 7Me-IEITC reduced the viability of the ECC-1 and KLE cancer cell-lines (IC(50)~2.5-10 μM) in a dose dependent fashion. 7Me-IEITC treatment caused mitochondrial transmembrane potential reduction, elevated the production of ROS, leading to activation of apoptosis in endometrial cancer KLE and ECC-1 cells. 7Me-IEITC treatment activated Bad, suppressed Bcl2 phosphorylation followed by PARP-1 deactivation and caspase 3 and 7 activation. 7Me-IEITC treatment arrested the progression of KLE cells in S-phase and caused CDC25 and cyclin-D1 downregulation. Pre-treatment with ascorbic acid abrogated 7Me-IEITC induced apoptosis in ECC-1 and KLE cells, suggesting that 7Me-IEITC mediated cytotoxicity is primarily through ROS production.
Conclusion: 7Me-IEITC demonstrated promising cytotoxic effects in endometrial cancer cell line model.
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| http://dx.doi.org/10.1016/j.ygyno.2012.04.041 | DOI Listing |
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