Polyamines Increase in Human Peripheral Blood and Bone Marrow Mononuclear Cells following Administration of Methylglyoxal bis(guanylhydrazone)

Maddox, Anne Marie; Keating, Michael J.; Freireich, Emil J.; Haddox, Mari K.

doi:10.1159/000238602

Cited by 2 publications

(1 citation statement)

References 25 publications

(26 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been suggested that the polyamine transporter may provide a useful means of directing cytotoxic agents to tumour cells in vivo [8]. Recently, Maddox and associates [22] showed an increase in the cellular content of MGBG following DFMO therapy in patients with haematological malignancies. MGBG is known to be transported by the polyamine uptake system [6].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of putrescine uptake by polypyridinium quaternary salts in B16 melanoma cells treated with difluoromethylornithine

Minchin

Martin

Summers

et al. 1989

Biochemical Journal

View full text Add to dashboard Cite

Several bipyridinium, tetrapyridinium and hexapyridinium quaternary salts have been found to be potent inhibitors of putrescine uptake into B16 melanoma cells which had previously been treated with difluoromethylornithine. In general, the potency of inhibitors increased as the number of quaternary centres increased. A relationship between the distance apart of the positively charged nitrogen atoms and the potency of the salts as inhibitors of uptake has been established by comparison with a number of diaminoalkanes. It was found that an inter-nitrogen distance of 0.6-0.7 nm or 1.0-1.1 nm was optimal for high activity. This finding is significant in determining structural features of the polyamine transport system.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of putrescine uptake by polypyridinium quaternary salts in B16 melanoma cells treated with difluoromethylornithine

Minchin

Martin

Summers

et al. 1989

Biochemical Journal

View full text Add to dashboard Cite

show abstract

Polyamines: from Molecular Biology to Clinical Applications

Jänne¹,

Alhonen²,

1991

View full text Add to dashboard Cite

The polyamines putrescine, spermidine and spermine represent a group of naturally occurring compounds exerting a bewildering number of biological effects, yet despite several decades of intensive research work, their exact physiological function remains obscure. Chemically these compounds are organic aliphatic cations with two (putrescine), three (spermidine) or four (spermine) amino or amino groups that are fully protonated at physiological pH values. Early studies showed that the polyamines are closely connected to the proliferation of animal cells. Their biosynthesis is accomplished by a concerted action of four different enzymes: ornithine decarboxylase, adenosylmethionine decarboxylase, spermidine synthase and spermine synthase. Out of these four enzyme, the two decarboxylases represent unique mammalian enzymes with an extremely short half life and dramatic inducibility in response to growth promoting stimuli. The regulation of ornithine decarboxylase, and to some extent also that of adenosylmethionine decarboxylase, is complex, showing features that do not always fit into the generally accepted rules of molecular biology. The development and introduction of specific inhibitors to the biosynthetic enzymes of the polyamines have revealed that an undisturbed synthesis of the polyamines is a prerequisite for animal cell proliferation to occur. The biosynthesis of the polyamines thus offers a meaningful target for the treatment of certain hyperproliferative diseases, most notably cancer. Although most experimental cancer models responds strikingly to treatment with polyamine antimetabolites--namely, inhibitors of various polyamine synthesizing enzymes--a real breakthrough in the treatment of human cancer has not yet occurred. It is, however, highly likely that the concept is viable. An especially interesting approach is the chemoprevention of cancer with polyamine antimetabolites, a process that appears to work in many experimental animal models. Meanwhile, the inhibition of polyamine accumulation has shown great promise in the treatment of human parasitic diseases, such as African trypanosomiasis.

show abstract

Polyamines Increase in Human Peripheral Blood and Bone Marrow Mononuclear Cells following Administration of Methylglyoxal bis(guanylhydrazone)

Cited by 2 publications

References 25 publications

Inhibition of putrescine uptake by polypyridinium quaternary salts in B16 melanoma cells treated with difluoromethylornithine

Inhibition of putrescine uptake by polypyridinium quaternary salts in B16 melanoma cells treated with difluoromethylornithine

Polyamines: from Molecular Biology to Clinical Applications

Contact Info

Product

Resources

About