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

Cheng, Fang LU ; Johnsson, Richard LU ; Nilsson, Jakob LU ; Fransson, Lars-Åke LU ; Ellervik, Ulf LU and Mani, Katrin LU (2009) In Cancer Letters 273. p.148-154
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Letters
volume
273
pages
148 - 154
publisher
Elsevier
external identifiers
  • WOS:000262583400017
  • PMID:18783879
  • Scopus:56349085463
ISSN
1872-7980
DOI
10.1016/j.canlet.2008.07.036
language
English
LU publication?
yes
id
47defcdf-914e-4907-b15f-807d31174a6c (old id 1243155)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18783879?dopt=Abstract
date added to LUP
2008-10-07 13:53:08
date last changed
2016-10-13 04:24:03
@misc{47defcdf-914e-4907-b15f-807d31174a6c,
  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.},
  author       = {Cheng, Fang and Johnsson, Richard and Nilsson, Jakob and Fransson, Lars-Åke and Ellervik, Ulf and Mani, Katrin},
  issn         = {1872-7980},
  language     = {eng},
  pages        = {148--154},
  publisher    = {ARRAY(0x8f859f0)},
  series       = {Cancer Letters},
  title        = {Potentiation of naphthoxyloside cytotoxicity on human tumor cells by difluoromethylornithine and spermine-NONOate.},
  url          = {http://dx.doi.org/10.1016/j.canlet.2008.07.036},
  volume       = {273},
  year         = {2009},
}