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

✍ Scribed by Rodney F. Minchin; Samuel Knight; Ajanthy Arulpragasam; Mirjana Fogel-Petrovic

Publisher: John Wiley and Sons
Year: 2006
Tongue: French
Weight: 133 KB
Volume: 118
Category: Article
ISSN: 0020-7136
DOI: 10.1002/ijc.21359

No coin nor oath required. For personal study only.

✦ Synopsis

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 lM) in human melanoma cells resistant to the drug. At higher concentrations, growth inhibition was seen in all cell lines, with IC 50 values ranging 2-180 lM. 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.

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