Potentiation of naphthoxyloside cytotoxicity on human tumor cells by difluoromethylornithine and spermine-NONOate.

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Abstract

Here we demonstrate a synergistic and tumor selective cytotoxic effect by combined treatment with naphthoxylosides, polyamine synthesis inhibitor, and polyamine based nitric oxide (NO) donor, using in vitro human tumor models. We have earlier reported that heparan sulfate priming naphthoxyloside, 2-(6-hydroxynaphthyl)-O-beta-d-xylopyranoside, which inhibits growth of human tumor cells in vitro and in vivo models, undergoes NO dependent cleavage and accumulates in the nuclei of tumor cells. Polyamine depletion using alpha-difluoromethylornithine (DFMO) increases both the number of NO sensitive sites in heparan sulfate and uptake of the polyamine based NO donor, spermineNONOate, thereby enhancing formation of growth-inhibitory NO induced heparan sulfate products with specific cytotoxic effect on tumor cells. We also show that peracetylation of xylosides doubles the antiproliferative effect towards human cancer cells by making these compounds more permeable to the cells.

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  • Cancer and Oncology
Original languageEnglish
Pages (from-to)148-154
JournalCancer Letters
Volume273
Publication statusPublished - 2009
Publication categoryResearch
Peer-reviewedYes