Document Detail


Silibinin prevents ultraviolet B radiation-induced epidermal damages in JB6 cells and mouse skin in a p53-GADD45α-dependent manner.
MedLine Citation:
PMID:  22166495     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Better preventive strategies are required to reduce ultraviolet (UV)-caused photodamage, the primary etiological factor for non-melanoma skin cancer (NMSC). Accordingly, here we examined the preventive efficacy of silibinin against UVB-induced photodamage using mouse epidermal JB6 cells and SKH1 hairless mouse epidermis. In JB6 cells, silibinin pretreatment protected against apoptosis and accelerated the repair of cyclobutane pyrimidine dimers (CPD) induced by moderate dose of UVB (50 mJ/cm(2)), which we are at risk of daily exposure. Silibinin also reversed UVB-induced S phase arrest, reducing both active DNA synthesizing and inactive S phase populations. In mechanistic studies, UVB-irradiated cells showed a transient upregulation of both phosphorylated (Ser-15 and Ser-392) and total p53, whereas silibinin pretreatment led to a more sustained upregulation and stronger nuclear localization of p53. Silibinin also caused a marked upregulation of GADD45α, a downstream target of p53, implicated in DNA repair and cell cycle regulation. Importantly, under p53 and GADD45α knockdown conditions, cells were more susceptible to UVB-induced apoptosis without any significant S phase arrest, and protective effects of silibinin were compromised. Similar to the in vitro results, topical application of silibinin prior to or immediately after UVB irradiation resulted in sustained increase in p53 and GADD45α levels and accelerated CPD removal in the epidermis of SKH1 hairless mice. Together, our results show for the first time that p53-mediated GADD45α upregulation is the key mechanism by which silibinin protects against UVB-induced photodamage and provides a strong rationale to investigate silibinin in reducing the risk and/or preventing early onset of NMSC.
Authors:
Srirupa Roy; Gagan Deep; Chapla Agarwal; Rajesh Agarwal
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-12-12
Journal Detail:
Title:  Carcinogenesis     Volume:  33     ISSN:  1460-2180     ISO Abbreviation:  Carcinogenesis     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-02     Completed Date:  2012-05-08     Revised Date:  2014-01-06    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  629-36     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / genetics,  radiation effects
Cell Cycle / drug effects
Cell Cycle Proteins / biosynthesis,  genetics,  metabolism*
Cell Line, Tumor
Mice
Mice, Hairless
Nuclear Proteins / biosynthesis,  genetics,  metabolism*
Pyrimidine Dimers / chemistry
RNA Interference
RNA, Small Interfering
S Phase Cell Cycle Checkpoints
Silymarin / pharmacology*
Skin / drug effects*,  pathology,  radiation effects*
Skin Neoplasms / drug therapy,  prevention & control
Tumor Suppressor Protein p53 / biosynthesis,  metabolism*
Ultraviolet Rays
Grant Support
ID/Acronym/Agency:
R01 CA140368/CA/NCI NIH HHS; R01 CA140368/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Gadd45a protein, mouse; 0/Nuclear Proteins; 0/Pyrimidine Dimers; 0/RNA, Small Interfering; 0/Silymarin; 0/Tumor Suppressor Protein p53; 4RKY41TBTF/silybin
Comments/Corrections

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


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