Document Detail

Evaluation of sphinganine and sphingosine as human breast cancer chemotherapeutic and chemopreventive agents.
MedLine Citation:
PMID:  17060688     Owner:  NLM     Status:  MEDLINE    
No comparative study of the effects of sphingolipid metabolites on proliferation and differentiation in normal human breast epithelial cells versus stem cells and tumorigenic cells has been reported. The purpose of this study was to evaluate the chemotherapeutic and chemopreventive potential of sphingoid bases (sphingosine and sphinganine) using a novel cell culture system of normal human breast epithelial cells (HBEC) developed from breast tissues of healthy women obtained during reduction mammoplasty (Type I HBEC with stem cell characteristics and Type II HBEC with basal epithelial cell phenotypes) and transformed tumorigenic Type I HBEC. The results show that sphinganine inhibited the growth and induced apoptosis of transformed tumorigenic Type I HBEC more potently than sphingosine (IC(50) for sphinganine 4 microM; sphingosine 6.4 microM). Both sphinganine and sphingosine at high concentrations (8-10 lM) arrested the cell cycle at G(2)/M. Sphinganine inhibited the growth and caused death of Type I HBEC more strongly than sphingosine. In comparison, Type II HBEC (normal differentiated cells) were less sensitive to the growth-inhibitory effects of sphingoid bases than Type I HBEC (stem cells) or transformed tumorigenic Type I HBEC, suggesting that sphingoid bases may serve as chemotherapeutic agents. At concentrations (0.05, 0.1, and 0.5 microM) that are below the growth-inhibitory range, sphingoid bases induced differentiation of Type I HBEC to Type II HBEC, as detected morphologically and via expression of a tumor suppressor protein, maspin, which is a marker of Type II HBEC. Thus, sphingoid bases may function as chemotherapeutic as well as chemopreventive agents by preferentially inhibiting cancer cells and eliminating stem cells from which most breast cancer cells arise.
Eun Hyun Ahn; Chia-Cheng Chang; Joseph J Schroeder
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Publication Detail:
Type:  Comparative Study; Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental biology and medicine (Maywood, N.J.)     Volume:  231     ISSN:  1535-3702     ISO Abbreviation:  Exp. Biol. Med. (Maywood)     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-10-24     Completed Date:  2006-12-05     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  100973463     Medline TA:  Exp Biol Med (Maywood)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1664-72     Citation Subset:  IM    
University of Pennsylvania School of Medicine, Department of Pathology and Laboratory Medicine, 506 Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104, USA.
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MeSH Terms
Apoptosis / drug effects*
Breast Neoplasms / pathology,  prevention & control
Cell Cycle / drug effects*
Cell Transformation, Neoplastic
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Inhibitory Concentration 50
Neoplastic Stem Cells
Sphingosine / analogs & derivatives*,  pharmacology*,  therapeutic use
Tumor Cells, Cultured
Reg. No./Substance:
0/Enzyme Inhibitors; 123-78-4/Sphingosine; 764-22-7/safingol

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