The uptake of exogenously administered radiolabeled polyamines by a rat prostate-derived tumor line, the Dunning R3327 MAT-Lu, and various normal tissues was studied. Pretreatment of tumor cells in vitro with alpha-difluoromethylornithine (DFMO), a polyamine synthesis inhibitor, resulted in a markedly enhanced uptake of both [14C]putrescine and [14 C]spermidine. The in vitro uptake of [14C]putr...

To ascertain the role of spermidine/spermine N-1-acetyl-transferase (SSAT; the rate-limiting enzyme in polyamine catabolism) in cell injury, cultured kidney (HEK 293) cells conditionally overexpressing SSAT were generated. The SSAT expression was induced and its enzymatic activity increased 24 h after addition of tetracycline and remained elevated over the length of the experiments. Induction o...

The cell cycle regulatory events that interface with polyamine requirements for cell growth have not yet been clearly identified. Here we use specific inhibitors of polyamine biosynthetic enzymes to investigate the effect of polyamine pool depletion on cell cycle regulation. Treatment of MALME-3M cells with either the ornithine decarboxylase inhibitor difluoromethylornithine or the S-adenosylme...

BACKGROUND Dietary polyamines have been shown to give a significant contribution to the body pool of polyamines. Knowing the levels of polyamines (putrescine, spermidine, and spermine) in different foods and the contribution of daily food choice to polyamine intake is of interest, due to the association of these bioactive amines to health and disease. OBJECTIVE To estimate polyamine intake an...

Intracellular polyamines are absolutely required for cell proliferation and many tumorshave abnormal requirements for polyamines. Therefore, the polyamine metabolic pathwayrepresents a rational target for antineoplastic intervention. A number of polyamine analoguesact as potent modulators of cellular polyamine metabolism and exhibit encouragingeffects against tumor growth in bot...

Activation of STAT3 (signal transducer and activator of transcription 3) plays a crucial role in cell survival and proliferation. The aim of the present study was to clarify the role of STAT3 signalling in the protection of polyamine-depleted intestinal epithelial cells against TNF-alpha (tumour necrosis factor-alpha)-induced apoptosis. Polyamine depletion by DFMO (alpha-difluoromethylornithine...

KEY POINTS Kainate receptor heteromerization and auxiliary subunits, Neto1 and Neto2, attenuate polyamine ion-channel block by facilitating blocker permeation. Relief of polyamine block in GluK2/GluK5 heteromers results from a key proline residue that produces architectural changes in the channel pore α-helical region. Auxiliary subunits exert an additive effect to heteromerization, and thus re...

Treatment of mouse lymphoma S49 cells with D,L-alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, depleted cellular polyamine levels and stopped cell growth. The cells were arrested predominantly in G1. Thus, polyamine depletion may lead to a regulatory growth arrest in S49 cells. We tested two hypotheses regarding the relationship of growth arrest mediated by polyam...

Natural polyamines, putrescine, spermidine and spermine are ubiquitous cell components essential for normal cellular functions and growth. Chemically these compounds are very simple organic aliphatic cations and fully protonated under physiological conditions. There is a strong correlation between proliferation rate of the cells and their polyamine contents. Adjustments of intracellular concent...