Document Detail

Enhancement of UVB radiation-mediated apoptosis by sanguinarine in HaCaT human immortalized keratinocytes.
MedLine Citation:
PMID:  16505117     Owner:  NLM     Status:  MEDLINE    
In this article, we studied the chemopreventive effects of sanguinarine on UVB-mediated responses in human HaCaT immortalized keratinocytes. For our studies, HaCaT cells were treated with a low dose (50 nmol/L) of sanguinarine for 24 hours followed by irradiation with UVB (15 or 30 mJ/cm2). Our data showed that UVB exposure, at both doses, resulted in decreased cell viability and increased apoptosis. Interestingly, pretreatment of the cells with sanguinarine caused a significant enhancement in the antiproliferative response of UVB. These responses on UVB and/or sanguinarine treatments were associated with (a) decrease in Bcl-2 and Bcl-X(L) and (b) increase in Bax, Bid, and Bak protein levels. Bax knockdown and Bcl-2 overexpression resulted in a rescue of HaCaT cells from sanguinarine-mediated apoptosis. DNA cell cycle analysis revealed that UVB treatment resulted in an accumulation of cells in the G2-M phase of the cell cycle, whereas pretreatment of sanguinarine resulted in a significant shift of cells in the S phase at a low UVB dose and a further accumulation of cells in the G2-M phase at a higher UVB dose. These effects on cell cycle were accompanied with modulations in the protein levels of cyclin (B1, E, and A) and cdc2 and cyclin-dependent kinase 1. Furthermore, sanguinarine treatment was found to result in significant modulations in p53, p66Shc, MsrA, and superoxide dismutase levels. Based on our data, we suggest the sanguinarine may protect skin cells from UVB-mediated damages via apoptotic elimination of damaged cells that escape programmed cell death and therefore possess a potential of clonal expansion.
Shannon Reagan-Shaw; Jorien Breur; Nihal Ahmad
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Molecular cancer therapeutics     Volume:  5     ISSN:  1535-7163     ISO Abbreviation:  Mol. Cancer Ther.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-02-28     Completed Date:  2006-05-04     Revised Date:  2012-05-28    
Medline Journal Info:
Nlm Unique ID:  101132535     Medline TA:  Mol Cancer Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  418-29     Citation Subset:  IM    
Department of Dermatology, University of Wisconsin, 25B Medical Science Center, 1300 University Avenue, Madison, WI 53706, USA.
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MeSH Terms
Adaptor Proteins, Signal Transducing / metabolism
Alkaloids / pharmacology*
Apoptosis / drug effects*
Cell Cycle / drug effects,  radiation effects
Cell Line, Transformed
Colony-Forming Units Assay
Cyclins / metabolism
Keratinocytes / drug effects*,  metabolism,  radiation effects
Methionine Sulfoxide Reductases
Oxidative Stress
Oxidoreductases / metabolism
Proto-Oncogene Proteins c-bcl-2 / metabolism
Radiation Tolerance / drug effects*
Radiation-Protective Agents / pharmacology*
Shc Signaling Adaptor Proteins
Superoxide Dismutase / metabolism
Tumor Suppressor Protein p53 / metabolism
Ultraviolet Rays
Grant Support
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Alkaloids; 0/Benzophenanthridines; 0/Cyclins; 0/Isoquinolines; 0/Proto-Oncogene Proteins c-bcl-2; 0/Radiation-Protective Agents; 0/SHC1 protein, human; 0/Shc Signaling Adaptor Proteins; 0/Tumor Suppressor Protein p53; 2447-54-3/sanguinarine; EC 1.-/Oxidoreductases; EC Dismutase; EC 1.8.4.-/Methionine Sulfoxide Reductases; EC sulfoxide reductase

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