Document Detail


The natural antioxidant alpha-lipoic acid induces p27(Kip1)-dependent cell cycle arrest and apoptosis in MCF-7 human breast cancer cells.
MedLine Citation:
PMID:  20580704     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Unlike normal cells, tumor cells survive in a specific redox environment where the elevated reactive oxygen species contribute to enhance cell proliferation and to suppress apoptosis. Alpha-lipoic acid, a naturally occurring reactive oxygen species scavenger, has been shown to possess anticancer activity, due to its ability to suppress proliferation and to induce apoptosis in different cancer cell lines. Since at the moment little information is available regarding the potential effects of alpha-lipoic acid on breast cancer, in the present study we addressed the question whether alpha-lipoic acid induces cell cycle arrest and apoptosis in the human breast cancer cell line MCF-7. Moreover, we investigated some molecular mechanisms which mediate alpha-lipoic acid actions, focusing on the role of the PI3-K/Akt signalling pathway. We observed that alpha-lipoic acid is able to scavenge reactive oxygen species in MCF-7 cells and that the reduction of reactive oxygen species is followed by cell growth arrest in the G1 phase of the cell cycle, via the specific inhibition of Akt pathway and the up-regulation of the cyclin-dependent kinase inhibitor p27(kip1), and by apoptosis, via changes of the ratio of the apoptotic-related protein Bax/Bcl-2. Thus, the anti-tumor activity of alpha-lipoic acid observed in MCF-7 cells further stresses the role of redox state in regulating cancer initiation and progression.
Authors:
Elena Dozio; Massimiliano Ruscica; Luca Passafaro; Giada Dogliotti; Liliana Steffani; Paola Marthyn; Alessandra Pagani; Germana Demartini; Daniele Esposti; Franco Fraschini; Paolo Magni
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-24
Journal Detail:
Title:  European journal of pharmacology     Volume:  641     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-07-15     Completed Date:  2010-10-28     Revised Date:  2010-12-13    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  29-34     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier B.V. All rights reserved.
Affiliation:
Department of Human Morphology and Biomedical Sciences Città Studi, via L. Mangiagalli 31, Università degli Studi di Milano, Milan, Italy. elena.dozio@unimi.it
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MeSH Terms
Descriptor/Qualifier:
Antioxidants / pharmacology*
Apoptosis / drug effects*
Biological Products / pharmacology*
Breast Neoplasms / pathology*
Cell Cycle / drug effects*
Cell Line, Tumor
Cell Proliferation / drug effects
Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
Down-Regulation / drug effects
Gene Expression Regulation, Neoplastic / drug effects
Humans
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Reactive Oxygen Species / metabolism
Signal Transduction / drug effects
Thioctic Acid / pharmacology*
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Biological Products; 0/Reactive Oxygen Species; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 62-46-4/Thioctic Acid; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt
Comments/Corrections
Erratum In:
Eur J Pharmacol. 2011 Jan 10;650(1):486
Note: Marthyn, Paola [added]

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


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