Document Detail

Development and characteristics of a human cell assay for screening agents for melanoma prevention.
MedLine Citation:
PMID:  17235241     Owner:  NLM     Status:  MEDLINE    
This paper describes the development and initial evaluation of a human cell assay to identify potentially efficacious agents for preventing melanoma. Four human cell lines were used: normal melanocytes, a radial growth-phase-like melanoma cell line (WM3211), a vertical growth-phase-like melanoma cell line (Lu1205), and 83-2c, a cell strain cloned from metastatic melanoma. Four endpoints were evaluated in ultraviolet B-treated cells: annexin V, human leukocyte antigen-DR; E-cadherin, and N-cadherin. Annexin V was induced by nimesulide, 4-hydroxyphenylretinamide, and difluoromethylornithine in ultraviolet-B-treated radial growth-phase-like melanoma cells. None of the agents inhibited human leukocyte antigen-DR expression in ultraviolet-B-treated radial growth-phase-like melanoma cells, the only cells that strongly expressed human leukocyte antigen-DR. E-cadherin was overexpressed only in radial growth-phase-like melanoma cells relative to melanocytes, and ultraviolet B exposure dramatically reduced this expression. E-cadherin was only induced by difluoromethylornithine in ultraviolet-B-treated radial growth-phase-like melanoma cells. N-cadherin was over- expressed in all melanoma cell lines relative to melanocytes. In this study, all candidate preventive agents inhibited N-cadherin in ultraviolet B-treated radial growth-phase-like melanoma cells. Four agents inhibited N-cadherin in ultraviolet B-treated vertical growth-phase-like melanoma cells. The mean ratios of N-cadherin to E-cadherin levels and specific endpoint responses for both the radial growth-phase-like melanoma and vertical growth-phase-like melanoma cells were used to rank the agents. Agents were evaluated at clinically relevant concentrations. The rankings were difluoromethylornithine>4-hydroxyphenylretinamide>nimesulide>9-cis-retinoic acid>polyphenon E. Diphenylhydramine, D-mannitol, and nordihydroguaiaretic acid were inactive. The results of these initial studies suggest that ultraviolet-B-treated radial growth-phase-like melanoma cells are the most responsive to chemopreventive agents, and may be the cell line of choice for screening melanoma prevention agents.
Eugene Elmore; Aarti Jain; Shazia Siddiqui; Nilou Tohidian; Frank L Meyskens; Vernon E Steele; John L Redpath
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Melanoma research     Volume:  17     ISSN:  0960-8931     ISO Abbreviation:  Melanoma Res.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-01-19     Completed Date:  2007-04-03     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  9109623     Medline TA:  Melanoma Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  42-50     Citation Subset:  IM    
Department of Radiation Oncology, University of California, Irvine, California 92697-2695, USA.
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MeSH Terms
Annexin A5 / analysis
Cadherins / analysis
Cell Line
Cell Line, Tumor
Foreskin / cytology
Infant, Newborn
Mass Screening / methods
Melanocytes / cytology*,  pathology
Melanoma / epidemiology,  prevention & control*
Reproducibility of Results
Skin Neoplasms / epidemiology,  prevention & control*
Ultraviolet Rays
Grant Support
Reg. No./Substance:
0/Annexin A5; 0/Cadherins

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