Document Detail


Evidence that bergapten, independently of its photoactivation, enhances p53 gene expression and induces apoptosis in human breast cancer cells.
MedLine Citation:
PMID:  19519316     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Psoralens (5-MOP and 8-MOP), a class of naturally occurring compounds, in combination with ultraviolect light are potent modulators of epidermal cell growth and differentiation. For a long time, photo-chemotherapy has been used in the treatment of psoriasis where it can reduce the number of cycling keratinocytes and decrease the IGF-1 receptors. However, the molecular mechanism of PUVA therapy remains unclear. In this study, we have evaluated, for the first time, in MCF-7 and SKBR-3 breast cancer cells the effects of 5-MOP (Bergapten), independently of its photoactivation, on the signalling pathways involved in cell cycle arrest and in apoptosis. Drug treatment induced a block in the G0/G1 phase and increased mRNA and protein levels of p53 and p21waf. These data correlate with a functional activation of caspase 8/caspase 9 together with DAPI staining and DNA ladder. Bergapten can transactivate p53 gene promoter in these cells and site-direct mutagenesis studies showed that the binding sequence of the nuclear factor NF-Y on p53 promoter is required for 5-MOP responsiveness. Besides, Bergapten increases NF-Y nuclear translocation through p38 MAPK activation. The same treatment impairs the PI3Kinase/AKT survival signal, in hormone-dependent MCF-7 cells even in the presence of IGF-I/E2 mitogenic factors. Here, we demonstrated that Bergapten, independently on the exposure to UV, generates membrane signalling pathways able to address apoptotic responses in breast cancer cells and to counteract the stimulatory effect of IGF-I/E2 on estrogen-receptor positive MCF-7 cell growth and progression.
Authors:
M L Panno; F Giordano; M G Palma; V Bartella; V Rago; M Maggiolini; D Sisci; M Lanzino; F De Amicis; S Andò
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Current cancer drug targets     Volume:  9     ISSN:  1873-5576     ISO Abbreviation:  Curr Cancer Drug Targets     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-12     Completed Date:  2009-09-01     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  101094211     Medline TA:  Curr Cancer Drug Targets     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  469-81     Citation Subset:  IM    
Affiliation:
Dept. of Cellular Biology, Faculty of Science, University of Calabria, 87036 Arcavacata di Rende, Cosenza, Italy.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*,  genetics
Breast Neoplasms / drug therapy*,  genetics
Cell Cycle / drug effects*
Cell Line, Tumor
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Estradiol / pharmacology
Female
Gene Expression
Humans
Insulin-Like Growth Factor I / antagonists & inhibitors
Methoxsalen / analogs & derivatives*,  pharmacology
Neoplasms, Hormone-Dependent / drug therapy*,  genetics
Photosensitizing Agents / pharmacology
Signal Transduction / drug effects*
Transcriptional Activation
Tumor Suppressor Protein p53 / genetics*,  metabolism
Ultraviolet Rays
p38 Mitogen-Activated Protein Kinases / metabolism
Chemical
Reg. No./Substance:
0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Photosensitizing Agents; 0/Tumor Suppressor Protein p53; 298-81-7/Methoxsalen; 484-20-8/5-methoxypsoralen; 50-28-2/Estradiol; 67763-96-6/Insulin-Like Growth Factor I; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases

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


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