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7 Methyl Indole Ethyl Isothiocyanate causes ROS mediated apoptosis and cell cycle arrest in endometrial cancer cells.
MedLine Citation:
PMID:  22561404     Owner:  NLM     Status:  Publisher    
OBJECTIVE: Chemotherapy options for advanced endometrial cancer are limited and newer therapeutic agents are urgently needed. This study describes the therapeutic potential of 7Metyl-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 was 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)~2.5-10μM) 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 caspases 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 lines model.
Katrin Kristjansdottir; Kyukwang Kim; Joong Sub Choi; Timothy C Horan; L Brard; Richard G Moore; Rakesh K Singh
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-1
Journal Detail:
Title:  Gynecologic oncology     Volume:  -     ISSN:  1095-6859     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0365304     Medline TA:  Gynecol Oncol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Inc.
Molecular Therapeutics Laboratory, Program in Women's Oncology, Department of Obstetrics and Gynecology, Women & Infants Hospital of Rhode Island, Alpert Medical School, Brown University, Providence, RI, 02905, USA.
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