Document Detail


Down-regulation of Bcl-2 and Akt induced by combination of photoactivated hypericin and genistein in human breast cancer cells.
MedLine Citation:
PMID:  19932626     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Presented experiment considers combination of genistein and photodynamic therapy with hypericin with a view to achieve higher therapeutic outcome in human breast adenocarcinoma cell lines MCF-7 and MDA-MB-231, both identified in our conditions as photodynamic therapy resistant. Since genistein is known to suppress Bcl-2 expression, we predicted that photodynamic therapy with hypericin might benefit from mutual therapeutic combination. In line with our expectations, combined treatment led to down-regulation of Bcl-2 and up-regulation of Bax in both cell lines as well as to suppression of Akt and Erk1/2 phosphorylation induced by photoactivated hypericin in MCF-7 cells. Although Akt and Erk1/2 phosphorylation was not stimulated by photodynamic therapy with hypericin in MDA-MB-231 cells, it was effectively suppressed in combination. Variations in cell death signaling favoring apoptosis were indeed accompanied by cell cycle arrest in G(2)/M-phase, activation of caspase-7, PARP cleavage and increased occurrence of cells with apoptotic morphology of nucleus. All these events corresponded with suppression of proliferation and significantly lowered clonogenic ability of treated cells. In conclusion, our results indicate that pre-treatment with tyrosine kinase inhibitor genistein may significantly improve the effectiveness of photodynamic therapy with hypericin in MCF-7 and MDA-MB-231 breast cancer cells.
Authors:
Peter Ferenc; Peter Sol?r; J?n Kleban; Jarom?r Mikes; Peter Fedorocko
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-10-28
Journal Detail:
Title:  Journal of photochemistry and photobiology. B, Biology     Volume:  98     ISSN:  1873-2682     ISO Abbreviation:  J. Photochem. Photobiol. B, Biol.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-02-03     Completed Date:  2010-04-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8804966     Medline TA:  J Photochem Photobiol B     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  25-34     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier B.V. All rights reserved.
Affiliation:
Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Saf?rik University, Moyzesova 11, 040 01 Kosice, Slovakia. peter.ferenc@upjs.sk
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MeSH Terms
Descriptor/Qualifier:
Breast Neoplasms / drug therapy*,  enzymology,  metabolism
Caspase 7 / metabolism
Cell Division
Cell Line, Tumor
Down-Regulation
Female
G2 Phase
Genistein / pharmacology*,  therapeutic use
Humans
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Perylene / analogs & derivatives*,  pharmacology,  therapeutic use
Phosphorylation
Photochemotherapy
Photosensitizing Agents / pharmacology*,  therapeutic use
Protein Kinase Inhibitors / pharmacology*,  therapeutic use
Proto-Oncogene Proteins c-akt / metabolism*
Proto-Oncogene Proteins c-bcl-2 / metabolism*
bcl-2-Associated X Protein / metabolism
Chemical
Reg. No./Substance:
0/Photosensitizing Agents; 0/Protein Kinase Inhibitors; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-2-Associated X Protein; 198-55-0/Perylene; 446-72-0/Genistein; 548-04-9/hypericin; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 3.4.22.-/Caspase 7

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


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