Document Detail


In vitro effects of 2-methoxyestradiol on morphology, cell cycle progression, cell death and gene expression changes in the tumorigenic MCF-7 breast epithelial cell line.
MedLine Citation:
PMID:  20193762     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the present study, the antiproliferative mechanism of action of 1 microM 2-methoxyestradiol (2ME) was investigated in the MCF-7 cell line. Measurement of intracellular cyclin B and cytochrome c protein levels, reactive oxygen species formation, cell cycle progression and apoptosis induction were conducted by means of flow cytometry. Morphological changes were evaluated using transmission electron microscopy and fluorescent microscopy by employing Hoechst 33342 and acridine orange. Gene expression changes were conducted by means of microarrays. 2ME-treated cells demonstrated an increase in cyclin B protein levels, hydrogen peroxide formation, intracellular levels of cytochrome c, as well as an increase in early and late stages of apoptosis. In addition, morphological data revealed the presence of autophagic processes. Fluorescent microscopy showed an increase in acridine orange staining and electron microscopy revealed an increase in vacuolar formation in 2ME-treated cells. The gene expression of several genes associated with mRNA translation, autophagy-related processes and genes involved in microtubule dynamics were affected. The study contributes to the mechanistic understanding of 2ME's growth inhibition in MCF-7 cells and highlights the possibility of both apoptotic and autophagic processes being activated in response to 2ME treatment in this cell line.
Authors:
B A Stander; S Marais; C J J Vorster; A M Joubert
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-01
Journal Detail:
Title:  The Journal of steroid biochemistry and molecular biology     Volume:  119     ISSN:  1879-1220     ISO Abbreviation:  J. Steroid Biochem. Mol. Biol.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-29     Completed Date:  2010-04-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9015483     Medline TA:  J Steroid Biochem Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  149-60     Citation Subset:  IM    
Copyright Information:
2010 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Physiology, University of Pretoria, Pretoria, South Africa.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / genetics,  ultrastructure
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Autophagy / drug effects
Breast Neoplasms / genetics,  ultrastructure*
Caspase 3 / deficiency
Cell Cycle / drug effects*
Cell Death / drug effects*
Cell Line, Tumor
Cell Shape / drug effects*
Cyclin B1 / metabolism
Cytochromes c / metabolism
Estradiol / analogs & derivatives*,  pharmacology
Female
Gene Expression Regulation, Neoplastic / drug effects*
Humans
Oligonucleotide Array Sequence Analysis
Reactive Oxygen Species / metabolism
Receptors, Estrogen / metabolism
Vacuoles / drug effects,  ultrastructure
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/CCNB1 protein, human; 0/Cyclin B1; 0/Reactive Oxygen Species; 0/Receptors, Estrogen; 362-07-2/2-methoxyestradiol; 50-28-2/Estradiol; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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