PMID: 6538500Mar 1, 1984Paper

Potentiation of 1,3-bis(2-chloroethyl)-1-nitrosourea cytotoxicity in 9L rat brain tumor cells by methylglyoxal-bis(guanylhydrazone), an inhibitor of S-adenosyl-L-methionine decarboxylase

European Journal of Cancer & Clinical Oncology
D T HungL J Marton

Abstract

Methylglyoxal-bis(guanylhydrazone) (MGBG), a potent inhibitor of the spermidine and spermine biosynthetic enzyme S-adenosyl-L-methionine decarboxylase, enhanced the cytotoxicity of 1,3-bis-(2-chlorethyl)-1-nitrosourea in 9L rat brain tumor cells in vitro, as measured by a colony-forming efficiency assay, by an amount that was approximately the same as the potentiation caused by the ornithine decarboxylase inhibitor alpha-difluoromethylornithine. Dose enhancement ratios at 10, 1 and 0.1% survival levels were approximately 1.3 for both inhibitors. 9L cells that were treated for 48 hr with 40 microM MGBG had putrescine, spermidine and spermine levels that were 112, 41 and 21%, respectively, of polyamine levels in control cells. MGBG treatment does not increase intracellular levels of decarboxylated S-adenosyl-L-methionine (AdoMet) as alpha-difluoromethylornithine treatment does. Elevated levels of decarboxylated AdoMet could modify intracellular methylation reactions and could affect the cytotoxicity of a chloroethylnitrosourea. Despite the fact that MGBG treatment caused a slight increase in intracellular levels of AdoMet, it is unlikely that this elevation will increase the amount of intracellular methylation. Thus it appears th...Continue Reading

References

Sep 1, 1979·International Journal of Radiation Oncology, Biology, Physics·D F DeenM E Williams
Sep 1, 1977·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·O HebyJ W Gray
Jan 14, 1972·Biochemical and Biophysical Research Communications·H G Williams-Ashman, A Schenone

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Citations

Mar 9, 1993·Biochemical Pharmacology·L Stjernborg, L Persson
Feb 6, 2003·International Journal of Cancer. Journal International Du Cancer·Tiina PasanenJarmo Wahlfors
Apr 15, 1986·Biochemical Pharmacology·H G Williams-Ashman, J Seidenfeld

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