Document Detail

Different pathways are involved in arsenic-trioxide-induced cell proliferation and growth inhibition in human keratinocytes.
MedLine Citation:
PMID:  20016248     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Arsenic is a carcinogen that is associated with an increased risk of human skin cancer. On the other hand, arsenic trioxide (As(2)O(3)) has potential anticancer activity against a wide range of carcinomas. The mechanisms involved in these two opposing processes remain unclear. METHODS: We used normal human keratinocytes (NHK), the human keratinocyte HaCaT cell line and human epidermal carcinoma cells (A431 cell line) to investigate potential pathways involved in the effects on cell proliferation and growth inhibition by different concentrations of As(2)O(3). RESULTS: At low concentrations (0.5-32 nM), As(2)O(3) enhanced keratinocyte proliferation and regulated the expression of about 172 genes. Among them, cell cycling pathway genes (including CDK4 and E2F1) were significantly upregulated. At high concentrations (0.5-10 microM), As(2)O(3) inhibited cell growth in NHK and HaCaT cells, but not in A431 cells. As(2)O(3) significantly induced NHK and HaCaT apoptosis through the activation of caspase-3, as well as cell cycle arrest at the G2-M phase. CONCLUSION: Our data suggest that different pathways are involved in As(2)O(3)-mediated proliferation and growth inhibition. In addition, skin carcinoma cells were resistant to As(2)O(3)-induced cell growth inhibition and apoptosis when compared to NHK and HaCaT cells. Therefore, As(2)O(3) may not be appropriate for treatment of skin carcinomas.
X Bi; J Gu; Z Guo; S Tao; Y Wang; L Tang; J Wu; Q Mi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-12-14
Journal Detail:
Title:  Skin pharmacology and physiology     Volume:  23     ISSN:  1660-5535     ISO Abbreviation:  Skin Pharmacol Physiol     Publication Date:  2010  
Date Detail:
Created Date:  2010-02-04     Completed Date:  2010-04-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101188418     Medline TA:  Skin Pharmacol Physiol     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  68-78     Citation Subset:  IM    
Copyright Information:
(c) 2009 S. Karger AG, Basel.
Department of Dermatology, Changhai Hospital, Second Military Medical University, Shanghai, PR China.
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MeSH Terms
Apoptosis / drug effects
Arsenicals / administration & dosage,  pharmacology*
Carcinoma, Squamous Cell / drug therapy*,  pathology
Caspase 3 / drug effects,  metabolism
Cell Cycle / drug effects
Cell Enlargement / drug effects
Cell Line
Cell Line, Tumor
Cell Proliferation / drug effects
Cells, Cultured
Dose-Response Relationship, Drug
Gene Expression Regulation / drug effects
Keratinocytes / drug effects*,  metabolism
Oxides / administration & dosage,  pharmacology*
Skin Neoplasms / drug therapy*,  pathology
Reg. No./Substance:
0/Arsenicals; 0/Oxides; 1327-53-3/arsenic trioxide; EC 3.4.22.-/Caspase 3

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