Effect of methylglyoxal-bis (guanylhydrazone), an inhibitor of spermidine and spermine synthesis, on cell cycle traverse

Olle Heby, Laurence J. Marton, Charles B. Wilson, Joe Gray

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Flow cytometric analysis of the cellular DNA content and high pressure liquid chromatographic analysis of the cellular concentration of the polyamines putrescine, spermidine and spermine have been performed on exponentially growing populations of rat brain tumor cells following treatment with methylglyoxal-bis(guanylhydrazone) (MeGAG). This drug has previously been found to be a potent inhibitor of S-adenosyl-l-methionine decarboxylase, the enzyme that catalyzes the initial step in spermidine and spermine biosynthesis. MeGAG was found to inhibit cell proliferation within one generation time. During this time it produced an increase in the fraction of cells with a 2C DNA content (cells in the G1 phase of the cell cycle). Continued accumulation of cells in the G1 phase occurred with sustained treatment. Drug treatment also resulted in a marked decrease in the cellular spermidine and spermine concentraions. Cells did not emerge from their G1-arrest after the addition of spermidine or fresh medium and apparently had become irreversibly blocked by the drug. We suggest that (1) growth inhibition by MeGAG was due to depletion of the cellular pools of spermidine and spermine, and that (2) the cells accumulated in the G1 phase of the cell cycle because of a possible requirement for spermidine and spermine during the subsequent phases (S, G2 and M), the period during which polyamine biosynthesis and accumulation take place in continuously dividing mammalian cells.

Original languageEnglish (US)
Pages (from-to)1009-1017
Number of pages9
JournalEuropean Journal of Cancer (1965)
Volume13
Issue number9
DOIs
StatePublished - 1977
Externally publishedYes

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Mitoguazone
Spermidine
Spermine
Cell Cycle
G1 Phase
Polyamines
Pharmaceutical Preparations
Putrescine
G2 Phase
DNA
S Phase
Brain Neoplasms
Cell Division
High Pressure Liquid Chromatography
Cell Proliferation

ASJC Scopus subject areas

  • Oncology

Cite this

Effect of methylglyoxal-bis (guanylhydrazone), an inhibitor of spermidine and spermine synthesis, on cell cycle traverse. / Heby, Olle; Marton, Laurence J.; Wilson, Charles B.; Gray, Joe.

In: European Journal of Cancer (1965), Vol. 13, No. 9, 1977, p. 1009-1017.

Research output: Contribution to journalArticle

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