Document Detail


Modulation of markers associated with aggressive phenotype in MDA-MB-231 breast carcinoma cells by sulforaphane.
MedLine Citation:
PMID:  19728765     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Metastasis as a complex process involves loss of adhesion, migration, invasion and proliferation of cancer cells. Sulforaphane (SFN) is one of naturally occurring cancer chemopreventive isothiocyanates found in cruciferous vegetables, consumption of which has been associated with reduced risk of cancer. In this study, we describe effect of SFN on various aspects determining invasive behavior of MDA-MB-231 human breast carcinoma cells. We studied modulation of molecules associated with epithelial to mesenchymal transition (EMT), hypoxic marker CA IX and mitochondrially located peripheral benzodiazepine receptor (PBR) using flow cytometry, gene expression of matrix metalloproteinases MMP1, 3, 7, 9, 14, transcription factors POU5F1 and Twist1 mRNA by RT PCR, and cytokine production by multiplex bead assay. SFN downregulated PBR and vimentin expression in a dose dependent manner, but significantly affected neither HIF-1alpha, nor CA IX protein expression, nor VEGF and GLUT1 mRNA levels. Among studied MMPs, MMP7 and MMP14 mRNA were downregulated while no apparent effect on MMP1, MMP3 and MMP9 was observed. Further, we found significant down regulation of Twist1 and POU5F1, transcription factors that mediate EMT and the self-renewal of undifferentiated embryonic stem cells. SFN reduced also the production of pro-inflammatory cytokines IL-1beta, IL-6, TNF-alpha, IFN-gamma, immunomodulating cytokine IL-4 and growth factors involved in angiogenesis PDGF and VEGF. Our study shows that SFN efficacy is associated with the reversal of several biological characteristics connected with EMT or implicated in the matrix degradation and extracellular proteolysis, as well as with reduced production of pro-inflammatory cytokines and pro-angiogenic growth factors in MDA-MB-231 cells.
Authors:
L Hunakova; O Sedlakova; D Cholujova; P Gronesova; J Duraj; J Sedlak
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neoplasma     Volume:  56     ISSN:  0028-2685     ISO Abbreviation:  Neoplasma     Publication Date:  2009  
Date Detail:
Created Date:  2009-09-04     Completed Date:  2009-11-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0377266     Medline TA:  Neoplasma     Country:  Slovakia    
Other Details:
Languages:  eng     Pagination:  548-56     Citation Subset:  IM    
Affiliation:
Tumor Immunology Laboratory, Cancer Research Institute, Bratislava, Slovak Republic. exonhun@savba.sk
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MeSH Terms
Descriptor/Qualifier:
Anticarcinogenic Agents / pharmacology*
Blotting, Western
Breast Neoplasms / drug therapy*,  metabolism*,  pathology
Cytokines / metabolism
Female
Flow Cytometry
Gene Expression Profiling
Humans
Oligonucleotide Array Sequence Analysis
Phenotype
RNA, Messenger / genetics,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Thiocyanates / pharmacology*
Tumor Cells, Cultured
Tumor Markers, Biological / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Anticarcinogenic Agents; 0/Cytokines; 0/RNA, Messenger; 0/Thiocyanates; 0/Tumor Markers, Biological; 4478-93-7/sulforafan

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