Concentration dependent effects of N1,N11-diethylnorspermine on melanoma cell proliferation

Minchin, Rodney F., Knight, Samuel, Arulpragasam, Ajanthy and Fogel-Petrovic, Mirjana (2006) Concentration dependent effects of N1,N11-diethylnorspermine on melanoma cell proliferation. International Journal of Cancer, 118 2: 509-512. doi:10.1002/ijc.21359


Author Minchin, Rodney F.
Knight, Samuel
Arulpragasam, Ajanthy
Fogel-Petrovic, Mirjana
Title Concentration dependent effects of N1,N11-diethylnorspermine on melanoma cell proliferation
Journal name International Journal of Cancer   Check publisher's open access policy
ISSN 0020-7136
Publication date 2006-01-01
Sub-type Article (original research)
DOI 10.1002/ijc.21359
Volume 118
Issue 2
Start page 509
End page 512
Total pages 4
Editor H zur Hausen
Place of publication United States
Publisher John Wiley & Sons, Inc.
Language eng
Subject C1
320501 Pharmaceutical Sciences and Pharmacy
730108 Cancer and related disorders
Abstract N-1, N-11-Diethylnorspermine (DENSPM) is a polyamine analog that is currently under investigation as a novel anticancer drug. Although it has shown promising preclinical activity, there has been large variation in responsiveness reported between different human cancers. During our studies into the causes of this variation, we observed a consistent increase in cell proliferation at low drug concentrations (<10 mu M) in human melanoma cells resistant to the drug. At higher concentrations, growth inhibition was seen in all cell lines, with IC50 values ranging 2-18 mu M. We hypothesized that DENSPM may mimic endogenous polyamines at low concentrations, supporting cell growth in resistant lines. We also observed that DENSPM downregulated polyamine transport in a manner similar to that for spermidine, a finding that confirms previous reports. Finally, DENSPM could rescue cells from growth arrest by the ornithine decarboxylase inhibitor difluoromethylornithine, which depletes intracellular polyamines. Taken together, these results suggest that DENSPM, at clinically relevant concentrations, can mimic endogenous polyamines and induce proliferation in resistant human melanoma cells. (c) 2005 Wiley-Liss. Inc.
Keyword Polyamine
Melanoma
Diethylnorspermine
Cell Proliferation
Cytotoxicity
Polyamine Analog N-1,n-11-diethylnorspermine
Spermidine-spermine N-1-acetyltransferase
Antitumor-activity
Carcinoma-cells
Lung-cancer
Drug-action
In-vitro
Phase-i
Growth
Gene
Q-Index Code C1

 
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Created: Wed, 15 Aug 2007, 19:52:51 EST