Effect of methylglyoxal bisguanylhydrazone on polyamine biosynthesis, growth, and differentiation of cultured keratinocytes

Proctor, Michael S.; Liu, Su Chin C.; Wilkinson, David

doi:10.1007/bf00404458

Cited by 9 publications

(2 citation statements)

References 14 publications

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“…The effect of MGBG can be totally prevented by concomitant treatment of the cells with equimolar concentrations of spermidine (Table 4). Spermidine inhibits both the uptake, and probably also the intracellular binding of MGBG, and it could be used in connection with MGBG treatment to alleviate drug toxicity, for the growth-inhibitory effects of MGBG in keratinocytes are reversible for several days (Proctor et al., 1980). In therapeutic use, this could provide a valuable means of avoiding skin irritation produced by an extensive accumulation of MGBG in the tissue (Weinstein ei al, 1981).…”

Section: Discussionmentioning

confidence: 99%

“…The combination of the two drugs could therefore also be effective in the treatment of psoriasis. Proctor, Liu & Wilkinson (1980) reported earlier that DNA accumulation and protein synthesis were inhibited in cultured human foreskin keratinocytes in response to MGBG treatment. The present study deals with the effects of DFMO and MGBG alone and in combination on cultured human keratinocytes derived from both normal skin and uninvolved psoriatic skin.…”

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confidence: 92%

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Effect of polyamine antimetabolites on cultured human keratinocytes from normal and uninvolved psoriatic skin

Käpyaho¹,

Kariniemi²,

Virtanen³

et al. 1984

Br J Dermatol

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We describe the effect of two polyamine antimetabolites on polyamine and macromolecule synthesis of cultured human keratinocytes obtained by suction blisters from normal skin and the uninvolved skin of psoriatic patients. The concentrations of spermidine and spermine steadily increased during the culture of normal keratinocytes in vitro, whereas the putrescine concentration showed only a transient rise at the beginning of the active growth phase. Treatment with difluoromethylornithine decreased the concentrations of putrescine and spermidine in both normal and uninvolved psoriatic keratinocytes, but had no effect on either DNA or protein synthesis. Methylglyoxal bis(guanylhydrazone) marginally decreased the levels of spermidine and spermine and significantly inhibited the DNA and protein synthetic activities. Pretreatment of uninvolved psoriatic keratinocytes with difluoromethylornithine enhanced the accumulation of methylglyoxal bis(guanylhydrazone), resulting in a profound inhibition of cellular macromolecule synthesis. This synergistic effect was not seen in normal keratinocytes. Thus, although no statistically significant difference was observed between the cells derived from normal and uninvolved psoriatic epidermis, the psoriatic keratinocytes appeared to be more sensitive to the action of polyamine antimetabolites. The inhibition of DNA and protein synthesis by methylglyoxal bis(guanylhydrazone) was prevented by concomitant treatment with spermidine.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 92%

Effect of polyamine antimetabolites on cultured human keratinocytes from normal and uninvolved psoriatic skin

Käpyaho¹,

Kariniemi²,

Virtanen³

et al. 1984

Br J Dermatol

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Polyamines

Allen¹

1989

Handbook of Experimental Pharmacology

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Mononuclear cell polyamine content associated with myeloid maturation in patients with leukemia during administration of polyamine inhibitors

et al. 1989

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Fourteen patients with acute leukemia in relapse were treated with difluoromethylornithine (DFMO) alone or in combination with methylglyoxal-bis(guanylhydrazone) (MGBG) as part of Phase I studies. Five patients included in the trial exhibited morphologic evidence of cellular differentiation during the course of treatment. In one patient who exhibited no blasts and a normal white blood cell differential at the end of treatment the mononuclear cell content of all three polyamines declined after an initial increase in spermidine and spermine content. In the other patients in whom the cellular maturation was less pronounced the mononuclear cell polyamine levels remained stable or increased over the treatment time. No absolute difference was apparent between the cellular polyamine levels detected in patients at the times of the greatest increase in per cent circulating neutrophils as compared to the cellular levels present in patients whose circulating mononuclear cell number were increasing. Circulating mononuclear cell putrescine, spermidine, and spermine levels varied over two orders of magnitude from patient to patient and the range of values detected in each state completely overlapped those present in the other. It does not appear from the present study that there is a consistent human leukemic cell polyamine content at which cellular differentiation occurs.

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Effect of methylglyoxal bisguanylhydrazone on polyamine biosynthesis, growth, and differentiation of cultured keratinocytes

Cited by 9 publications

References 14 publications

Effect of polyamine antimetabolites on cultured human keratinocytes from normal and uninvolved psoriatic skin

Effect of polyamine antimetabolites on cultured human keratinocytes from normal and uninvolved psoriatic skin

Polyamines

Mononuclear cell polyamine content associated with myeloid maturation in patients with leukemia during administration of polyamine inhibitors

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