Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “polyamines”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,045 records · Page 58Linked to original sources
PubMed2003

RhoA stimulates IEC-6 cell proliferation by increasing polyamine-dependent Cdk2 activity.

Although RhoA plays an important role in cell proliferation and in Ras transformation in fibroblasts and mammary epithelial cells, its role in intestinal epithelial cells (IEC) is unknown. In a previous study (Ray RM, Zimmerman BJ, McCormack SA, Patel TB, and Johnson LR. Am J Physiol Cell Physiol 276: C684-C691, 1999), we showed that polyamine depletion [dl-alpha-difluoromethylornithine (DFMO) treatment] strongly inhibits the proliferation of IEC. In this report, we examined the effect of RhoA on IEC-6 cell proliferation and whether polyamine depletion inhibits cell proliferation in the presence of constitutively active RhoA. Constitutively active RhoA and vector-transfected IEC-6 cell lines were grown in the presence or absence of DFMO, which causes polyamine depletion by inhibiting ornithine decarboxylase, the first rate-limiting step in polyamine synthesis. Constitutively active RhoA significantly increased the rate of cell proliferation. These cells also lost contact inhibition and formed conspicuous foci when they were fully confluent. Decreased p21Waf1/Cip1 expression and increased cyclin-dependent kinase (Cdk2) mRNA levels and activity accompanied the increased proliferation. The inhibition of p21Waf1/Cip1 was independent of p53. There was no activation of the Ras-Raf-MEK-ERK pathway in the RhoA-transfected cell line. Polyamine depletion totally prevented the effect of activated RhoA on IEC-6 cell proliferation, focus formation, and Cdk2 expression. The stability of mRNA and protein for Cdk2 and p21Waf1/Cip1 in V14-RhoA cells was not significantly different from that of vector-transfected cells. In conclusion, RhoA activation decreased p21Waf1/Cip1 expression and increased basal and serum-induced ornithine decarboxylase activity, Cdk2 expression, Cdk2 protein, and Cdk2 activity, leading to the stimulation of IEC proliferation and transformation. Polyamine depletion totally prevented RhoA's effect on proliferation by decreasing Cdk2 expression and activity.

Animals↗
PubMed1993

Polyamines are necessary for cell migration by a small intestinal crypt cell line.

Studies from our laboratory have shown that polyamines are essential for the normal repair of duodenal erosions induced in vivo in a rat stress-ulcer model. In that model, the inhibition of ornithine decarboxylase, a rate-limiting enzyme of polyamine biosynthesis, with alpha-difluoromethylornithine (DFMO) almost entirely prevented healing. Healing could be restored by oral polyamines. In this paper, we have investigated whether the polyamines are required for the early stages of epithelial restitution using an IEC-6 cell culture model of cell migration. Treatment of the cells with DFMO for 4 days reduced cell migration 80%. Migration could be restored to normal by concomitant treatment with putrescine (PUT), spermidine (SPD), or spermine (SPM), but not by their addition during the migration period (6 h) only. If DFMO treatment was not begun until the migration period, it still reduced cell migration 20%, and this deficit could not be restored by concomitant addition of the polyamines. Intracellular polyamine levels at these times, i.e., 6 h or 4 days, were an important factor in these results. Only PUT was undetectable after 6 h of DFMO. SPD and SPM were still at normal levels at 6 h. SPD was undetectable at 4 days, but SPM was still at 40% of normal. These data give added importance to PUT because its absence reduced cell migration after only 6 h, while SPD and SPM were still present in normal amounts. Perhaps exogenous SPD and SPM restored cell migration when present with DFMO for 4 days treatment primarily because they contributed to intracellular PUT through the acetyltransferases.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1997

Polyamines are important for attachment of IEC-6 cells to extracellular matrix.

The inhibition of ornithine decarboxylase, a rate-limiting enzyme of polyamine biosynthesis, with alpha-difluoromethylornithine in IEC-6 cells (small intestinal crypt cell line) reduces cell migration by 70%, inhibits protein cross-linking, and affects the cytoskeletal assembly. The current study examines the effects of intracellular polyamine depletion on attachment of IEC-6 cells to different matrices. Polyamine deficiency inhibited cell attachment to plastic, laminin, fibronectin, collagen IV, and Matrigel by different extents. Intracellular putrescine restored attachment to all matrices. The presence of a specific inhibitor of protein cross-linking also inhibited attachment to laminin in a dose-dependent manner. The inhibition of cell attachment to plastic and Matrigel was correlated with the inhibition of cell migration. Immunofluorescence studies showed that polyamines are essential for the correct expression of the integrin subunit alpha 2 but not for the expression of the alpha 1-subunit. This study demonstrates that polyamines are important for cell attachment and expression of the integrin alpha 2 beta 1, a putative receptor for collagen and laminin. The impairment of protein cross-linking and the inhibition of the expression of cell surface receptors that bind extracellular matrix (ECM) proteins may be part of the mechanism by which polyamine deficiency retards cell migration in the small intestine.

Animals↗
PubMed1999

Polyamine depletion is associated with an increase in JunD/AP-1 activity in small intestinal crypt cells.

Activator protein 1 (AP-1) is a group of dimeric transcription factors composed of protooncogene (Jun and Fos) subunits that bind to a common DNA site, the AP-1 binding site. The proteins of c-Jun, JunB, and Fos are essential for initiation of the cell cycle. Conversely, the activation of the junD gene slows cell growth in some cell types. The current study tests the hypothesis that polyamines influence cell growth by altering the balance of positive and negative Jun/AP-1 activities in intestinal epithelial cells. Studies were conducted in the IEC-6 cell line derived from rat small intestinal crypt cells. Administration of alpha-difluoromethylornithine (DFMO), a specific inhibitor for polyamine synthesis, for 4 and 6 days completely depleted cellular polyamine levels, while AP-1 binding activity was significantly increased. Spermidine, when given together with DFMO, restored AP-1 binding activity toward normal. The increased AP-1 complexes in polyamine-deficient cells were dramatically supershifted by the anti-JunD antibody but not by antibodies against c-Jun, JunB, or Fos proteins. There were significant increases in JunD mRNA and protein in DFMO-treated cells, although expression of the c-fos, c-jun, and junB genes decreased. The increase in JunD/AP-1 activity in DFMO-treated cells was associated with a significant decrease in cell division. Exposure of control quiescent cells to 5% dialyzed serum increased c-Jun/AP-1 but not JunD/AP-1 activities. DFMO prevented the stimulation of c-Jun/AP-1 activity induced by 5% dialyzed serum. These results indicate that 1) polyamine depletion is associated with an increase in AP-1 binding activity and 2) the increase in AP-1 activity in the DFMO-treated cells was primarily contributed by an increase in the JunD/AP-1. These findings suggest that polyamines regulate cell growth at least partially by modulating the balance of positive and negative Jun/AP-1 activities in the intestinal mucosa.

Animals↗
PubMed2001

Polyamine depletion arrests growth of IEC-6 and Caco-2 cells by different mechanisms.

The polyamines spermidine and spermine and their precursor, putrescine, are required for the growth and proliferation of eukaryotic cells. This study compares and contrasts growth arrest caused by polyamine depletion in the untransformed IEC-6 cell line with that in the p53-mutated colon cancer Caco-2 cell line. Cells were grown in the presence or absence of alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase, the first rate-limiting enzyme in the synthesis of polyamines. Depletion of polyamines inhibited the growth of both cell lines equally and over the same time frame. However, whereas IEC-6 cells were arrested in the G(1) phase of the cell cycle, there was no accumulation of Caco-2 cells in any particular phase. In IEC-6 cells, growth arrest was accompanied by elevated levels of p53 and p21(Waf1/Cip1) (p21). There were no changes in p53 levels in Caco-2 cells. Levels of p21 increased in Caco-2 cells on day 2 without any effect on cell cycle progression. The amount of cyclin-dependent kinase (Cdk)2 protein was unchanged by polyamine depletion in both cell lines. However, the activity of Cdk2 was significantly inhibited by DFMO in IEC-6 cells. These data suggest that in the untransformed IEC-6 cells the regulation of Cdk2 activity and progression through the cell cycle are p53- and p21 dependent. Growth arrest in the p53-mutated Caco-2 line after polyamine depletion occurs by a different, yet unknown, mechanism.

CDC2-CDC28 Kinases↗
PubMed1976

Polyamine synthesis in liver and kidney of flounder in response to methylmercury.

The effect of methylmercury administration on polyamine synthesis was studied in the liver and kidney of the winter flounder (Pseudopleuronectes americanus). A single injection of methylmercury resulted in five- and sevenfold elevations of ornithine decarboxylase activity in the liver and kidney within 15 and 45 h, respectively. There were elevations of both putrescine- and spermidine-stimulated S-adenosylmethionine decarboxylase activities (approximately 1.5-fold) in both tissues. Evaluation of the polyamine accumulation patterns in these tissues indicated that in the liver all three polyamines increased in concentration until 48 h and then decline. In the kidney, the concentration of putrescine increased steadily until it was 200% of control at 72 h and then declined. Spermidine concentration decreased throughout the time studied and was 17% of control at 1 wk. There was no significant change in the concentration of spermine throughout the period studied. The changes in the polyamine pools and in the activities of the polyamine biosynthetic enzymes after methylmercury administration are consistent with an involvement of the polyamines in the recovery phase to a toxic dose of methylmercury.

Adenosylmethionine Decarboxylase↗
PubMed2000

A cortisol surge mediates the enhanced polyamine synthesis in porcine enterocytes during weaning.

This study was conducted to determine whether a cortisol surge mediates the enhanced expression of intestinal ornithine decarboxylase (ODC) in weanling pigs. Piglets were nursed by sows until 21 days of age, when 40 pigs were randomly assigned into one of four groups (10 animals/group). Group 1 continued to be fed by sows, whereas groups 2-4 were weaned to a corn and soybean meal-based diet. Weanling pigs received intramuscular injections of vehicle solvent (sesame oil), RU-486 (a potent blocker of glucocorticoid receptors; 10 mg/kg body wt), and metyrapone (an inhibitor of adrenal cortisol synthesis; 5 mg/kg body wt), respectively, 5 min before weaning and 24 and 72 h later. At 29 days of age, pigs were used to prepare jejunal enterocytes for ODC assay and metabolic studies. To determine polyamine (putrescine, spermidine, and spermine) synthesis, enterocytes were incubated for 45 min at 37 degrees C in 2 ml Krebs-bicarbonate buffer containing 1 mM [U-(14)C]arginine, 1 mM [U-(14)C]ornithine, 1 mM [U-(14)C]glutamine, or 1 mM [U-(14)C]proline plus 1 mM glutamine. Weaning increased intestinal ODC activity by 230% and polyamine synthesis from ornithine, arginine, and proline by 72-157%. Arginine was a quantitatively more important substrate than proline for intestinal polyamine synthesis in weaned pigs. Administration of RU-486 or metyrapone to weanling pigs prevented the increases in intestinal ODC activity and polyamine synthesis, reduced intracellular polyamine concentrations, and decreased villus heights and intestinal growth. Our results demonstrate an essential role for a cortisol surge in enhancing intestinal polyamine synthesis during weaning, which may be of physiological importance for intestinal adaptation and remodeling.

Animals↗
PubMed2004

Polyamine synthesis inhibition attenuates vascular smooth muscle cell migration.

Vascular smooth muscle cell migration, occurring after intimal injury, is a substantial clinical problem in atherosclerosis and restenosis after stenting. Here we investigate the effects of polyamine synthesis inhibition on vascular smooth muscle cell migration after maximal and submaximal growth stimulation with PDGF-AB or FCS. Vascular smooth muscle cells were obtained from mouse aorta explants. These cells coexpressed smooth muscle alpha-actin, PDGFRalpha and PDGFRbeta as demonstrated by immunocytochemistry. Treatment with a high (100 ng/ml) concentration of PDGF-AB stimulated DNA synthesis 6-fold and markedly elevated cell migration. PDGF-AB (100 ng/ml) increased cellular spermidine concentration 2-fold, but had no effect on spermine or putrescine levels. Treatment with the polyamine synthesis inhibitors CGP48664 (1 microM) and DFMO (5 mM) prevented the PDGF-AB-induced increase in spermidine and reduced spermine concentrations, but had no effect on PDGF-AB-stimulated DNA synthesis or cell migration. Cell migration after submaximal stimulation with either PDGF-AB (8 ng/ml) or FCS (8%) was, however, inhibited by the polyamine synthesis blockers. In summary, these data show that polyamine synthesis inhibition attenuates vascular smooth muscle cell migration under submaximal growth-stimulating conditions, suggesting that polyamines participate in regulation of cell migration and that treatment with polyamine synthesis inhibitors might reduce vascular smooth muscle cell migration after intimal injury.

Actins↗
PubMed1989

Polyamines mediate androgenic stimulation of calcium fluxes and membrane transport in rat heart myocytes.

The androgenic steroid hormone testosterone induced an early (less than 30-60 seconds) stimulation of endocytosis, hexose transport, and amino acid transport, monitored by the temperature-sensitive uptake of horseradish peroxidase, 2-deoxyglucose, and alpha-aminoisobutyrate, respectively, in rat ventricle cubes and acutely isolated ventricular myocytes. This stimulation was time- and concentration-dependent and was maximal at 10(-9) to 10(-8) M testosterone, consistent with androgen-receptor mediation. EGTA (2.5 mM), La3+ (1 mM), and verapamil (100 microM) ablated the hormonal response. The calcium ionophore A23187 (10 microM) induced an acute stimulation of endocytosis, amino acid transport, and hexose transport which was not further increased by testosterone (10(-8) M), suggesting a common effector pathway. Testosterone (10(-8) M) also evoked a rapid (less than 30 seconds) stimulation of 45Ca influx and efflux. Testosterone (10(-8) M) induced a rapid (less than 5 seconds) transient increase in ornithine decarboxylase (ODC) activity peaking (twofold to threefold) at 60 seconds, and an early (15 seconds) transient accumulation of polyamines peaking at 60 seconds in isolated myocytes. The specific, irreversible ODC inhibitor alpha-difluoromethylornithine (DFMO, 5-10 mM) blocked the testosterone-evoked increase in ODC activity and polyamine levels and the stimulation of Ca2+ fluxes, endocytosis, hexose transport, and amino acid transport. Putrescine (0.5-1 mM), the ODC product, reversed DFMO inhibition and restored the increase in polyamines, 45Ca fluxes, and Ca2+-dependent membrane transport processes. These results demonstrate that rapid, transient ODC-regulated polyamine synthesis is essential for androgenic stimulation of Ca2+ fluxes and membrane transport processes in ventricular myocytes. These findings support a model for signal transduction in which newly synthesized polyamines serve as intracellular messengers to regulate transmembrane Ca2+ movements, Ca2+-dependent membrane transport functions, and other Ca2+- and polyamine-sensitive processes in cardiac myocytes.

Amino Acids↗
PubMed2003

Polyamines in cultured rabbit corneal cells.

PURPOSE: To determine whether polyamines are present in corneal cells, whether corneal cell polyamines can be depleted by blocking the first rate-limiting enzyme in the polyamine synthesis pathway, ornithine decarboxylase (ODC), and whether polyamines are required for proliferation in all three corneal cell types. METHODS: Cultured corneal epithelial cells, keratocytes, and endothelial cells were exposed to the specific ODC blocker difluoromethylornithine (DFMO), and ODC activity, intracellular polyamine concentrations, and cell proliferation were measured. RESULTS: DFMO blocked ODC activity in a dose- and time-dependent manner in all three cell types. DFMO treatment completely depleted putrescine and spermidine by 2 days and also significantly depleted spermine. DFMO treatment also inhibited cell growth in all three cell types and this inhibition could be completely reversed by adding exogenous putrescine to the culture medium. CONCLUSIONS: Polyamines are present in all cell types of the cornea, their formation is catalyzed at least in part by ODC, and they are an important component of corneal cell proliferation.

Animals↗
PubMed1987

Polyamines mediate uncontrolled calcium entry and cell damage in rat heart in the calcium paradox.

Brief perfusion of heart with calcium-free medium renders myocardial cells calcium-sensitive so that readmission of calcium results in uncontrolled Ca2+ entry and acute massive cell injury (calcium paradox). We investigated the hypothesis that polyamines may be involved in the mediation of abnormal Ca2+ influx and cell damage in the calcium paradox. The isolated perfused rat heart was used for these studies. Calcium-free perfusion promptly (less than 5 min) decreased the levels of polyamines and the activity of their rate-regulating synthetic enzyme, ornithine decarboxylase (ODC), and calcium reperfusion abruptly (less than 15-180 s) increased these components. alpha-Difluoromethylornithine (DFMO), a specific suicide inhibitor of ODC, suppressed the calcium reperfusion-induced increase in polyamines and the concomitant increase in myocardial cellular 45Ca influx, loss of contractility, release of cytosolic enzymes, myoglobin, and protein, and structural lesions. Putrescine, the product of ODC activity, nullified DFMO inhibition and restored the calcium reperfusion-induced increment in polyamines and the full expression of the calcium paradox. Putrescine itself enhanced the reperfusion-evoked release of myoglobin and protein in the absence of DFMO. Hypothermia blocked the changes in heart ODC and polyamines induced by calcium-free perfusion and calcium reperfusion and prevented the calcium paradox. These results indicate that rapid Ca2+-directed changes in ODC activity and polyamine levels are essential for triggering excessive transsarcolemmal transport of Ca2+ and explosive myocardial cell injury in the calcium paradox.

Animals↗
PubMed1993

Enhanced stimulus-secretion coupling in polyamine-depleted rat insulinoma cells. An effect involving increased cytoplasmic Ca2+, inositol phosphate generation, and phorbol ester sensitivity.

To extend previous observations on the role of polyamines in insulin production, metabolism, and replication of insulin-secreting pancreatic beta cells, we have studied the role of polyamines in the regulation of the stimulus-secretion coupling of clonal rat insulinoma cells (RINm5F). For this purpose, RINm5F cells were partially depleted in their polyamine contents by use of the specific ornithine decarboxylase inhibitor difluoromethylornithine (DFMO), which led to an increase in cellular insulin and ATP contents. Analysis of different parts of the signal transduction pathway revealed that insulin secretion and the increase in cytoplasmic free Ca2+ concentration ([Ca2+]i) after K(+)-induced depolarization were markedly enhanced in DFMO-treated cells. These effects were paralleled by increased voltage-activated Ca2+ currents, as judged by whole-cell patch-clamp analysis, probably reflecting increased channel activity rather than elevated number of channels per cell. DFMO treatment also rendered phospholipase C in these cells more sensitive to the muscarinic receptor agonist carbamylcholine, as evidenced by enhanced generation of inositol phosphates, increase in [Ca2+]i and insulin secretion, despite an unaltered ligand binding to muscarinic receptors and lack of effect on protein kinase C activity. In addition, the tumor promoter 12-O-tetradecanoylphorbol 13-acetate, at concentrations suggested to be specific for protein kinase C activation, evoked an increased insulin output in polyamine-deprived cells compared to control cells. The stimulatory effects of glucose or the cyclic AMP raising agent theophylline on insulin release were not increased by DFMO treatment. In spite of increased binding of sulfonylurea in DFMO-treated cells, there was no secretory response or altered increase in [Ca2+]i in response to the drug in these cells. It is concluded that partial polyamine depletion sensitizes the stimulus-secretion coupling at multiple levels in the insulinoma cells, including increased voltage-dependent Ca2+ influx and enhanced responsiveness to activators of phospholipase C and protein kinase C. In their entirety, our present results indicate that the behavior of the stimulus-secretion coupling of polyamine-depleted RINm5F insulinoma cells changes towards that of native beta cells, thus improving the usefulness of this cell line for studies of beta cell insulin secretion.

Adenosine Triphosphate↗
PubMedDate not supplied

Effect of an elemental vs a complex diet on polyamine metabolism in rat isolated enterocytes.

BACKGROUND: Polyamines play an important role in the proliferation and differentiation of enterocytes. Ornithine decarboxylase (ODC) is the rate-limiting enzyme for polyamine biosynthesis. Elemental diets, providing easily absorbable nutrients such as free amino acids, are used in clinical practice to treat growth failure and malnutrition. They are very different from complex diets normally consumed. Little information is available about the influence of elemental diets on metabolic capacities of enterocytes. This study was undertaken in rats to assess the effects on polyamine metabolism of an elemental diet compared with a complex diet. METHODS: Rats were fed the elemental diet (group ED) or the control diet (group C) for 14 days. The dietary intakes were isocaloric and isonitrogenous in groups C and ED. Villous enterocytes were then isolated and metabolic capacities or enzyme activities were assessed. RESULTS: Both the enterocyte capacity to decarboxylate ornithine through ODC (measured in viable enterocytes) and ODC activity (measured in homogenates) were severely decreased in group ED. The polyamine content in enterocytes, however, was maintained at a similar level in both groups. This coincided with a decrease in the main enzymatic activity responsible for putrescine catabolism (ie, diamine oxidase activity) in group ED. CONCLUSIONS: Although nutrition manipulation was shown to alter polyamine biosynthesis in this study, the polyamine homeostasis was probably maintained, at least in part, through down-regulation of diamine oxidase.

Amine Oxidase (Copper-Containing)↗
PubMed1981

Levels of polyamines and nucleic acids in human breast carcinoma.

Polyamine and nucleic acid levels were determined in normal human breasts, in primary infiltrating ductal carcinoma breasts, in the uninvolved tissues of the same carcinoma-bearing breasts and in the urine of the same patients. The results showed that the production of polyamines in the carcinoma tissue is significantly higher than in normal tissue; the presence of a carcinoma in the breast does not modify the levels of polyamines and nucleic acids in the surrounding uninvolved tissue; spermidine and spermine are correlated both with DNA and RNA in the carcinoma; the urinary polyamine levels in the carcinoma-bearing patients were not significantly different from that of controls. There appeared to be a close relationship between polyamine biosynthesis and tumoral mammary cell development and a very fine control between the biosynthesis of both spermidine and spermine and nucleic acids. In addition, the localized solid breast carcinoma, with non-proven metastases, did not provoke an increase in polyamine excretion.

Adult↗
PubMed1985

Oxidation of oxalate and polyamines by rat peroxisomes.

During renal failure, polyamines and oxalate levels are elevated in the serum and the glomerular filtrate and are dumped by the kidney. Both of these compounds can be catabolized by oxidative reactions. We have, therefore, investigated the intracellular distribution of oxalate oxidase and of a polyamine oxidase in normal female rat kidney and liver. Polyamine oxidase was demonstrable, using spermidine as substrate in the cerous peroxyhydrate procedure of Briggs et al., in peroxisomes of kidney tubule cells and of hepatocytes. Oxalate oxidase could not be studied with this technique due to precipitation of cerium oxalate in the incubation medium. To demonstrate oxalate oxidase, and to confirm the polyamine oxidase localization, we incubated aldehyde-fixed tissue in a diaminobenzidine medium at pH 8, following the approach of Veenhuis et al., in which oxidases are demonstrated by virtue of their production of H2O2, which then serves as a substrate for endogenous catalase. Using oxalate or spermidine as substrate with this approach, we found reaction product in typical renal peroxisomes; we also found reaction product, with the polyamine substrate, in hepatocyte peroxisomes. To strengthen the conclusion that the oxidases themselves are present in peroxisomes, we used a light microscopic method, based on the tetrazolium procedures of Allen and Beard to demonstrate polyamine and oxalate oxidase activities in bodies with the distribution of renal peroxisomes.

Animals↗
PubMed2005

Antioxidative properties of natural polyamines and dimethylsilane analogues.

Structural analogues of natural polyamines, which contain a -Si(CH3)2 group in the central carbon chain, have previously been found to be cytotoxic to various tumor cell lines in vitro and to inhibit tumor cell growth in experimentally grafted animals. In the present study, the antioxidative properties of dimethylsilane polyamine analogues were analyzed in comparison with the natural polyamines. Reactivities of these various polyamines against superoxide anions (generated from the hypoxanthine/xanthine oxidase reaction) and peroxyl radicals (produced from the thermal decomposition of water-soluble 2,2'-azo-bis-[2-amidinopropane] hydrochloride) were investigated. The dimethysilane analogues, and more particularly the hexamine derivative, exhibited the highest scavenging efficiency towards these two reactive oxygen species (ROS). Furthermore, analysis of their ability to prevent hydroxyl radical formation and to trap this ROS showed that the efficiency of the hexamine as a metal chelator and hydroxyl radical scavenger is similar to that of spermine. The higher antioxidant efficiency of the dimethylsilane polyamine analogues with respect to spermidine, together with their ability to displace this polyamine, essential for the promotion of cell growth, from its cellular anionic binding sites that are particularly prone to oxidation, could be biologically relevant and contribute to their in vivo cytotoxic effect and anti-tumor activity. Further experiments will be necessary to demonstrate clearly the relationship between their antioxidant properties and their antiproliferative effects.

Antioxidants↗
PubMed1975

Polyamines in cystic fibrosis.

Polyamine concentrations have been measured in blood samples from a series of cystic fibrosis (CF) patients and control subjects. Analyses were made by a fluorometric method, in which the amines were reacted with dansyl chloride and separated by thin layer chromatography on Kieselguhr. There was no significant difference between the polyamine concentrations of blood samples from CF patients and control subjects. Also, the spermidine-spermine ratio was similar in both groups. Polyamines were also analyzed in exocrine fluids, and although none could be detected in either CF or control sweat or saliva, significant amounts of spermine and spermidine were present in all samples of bile and duodenal fluids. It thus seems likely that the biliary route is a significant pathway in the human for excretion of polyamines. The observation that polyamines are excreted in considerable concentrations via the bile in children may be of interest in view of the reports of elevated urinary polyamine concentrations in neoplastic states. Since measurable amounts of spermine and spermidine were detected in all six bile preparations available for this study, analysis of these substances in bile may be of benefit in particular cases.

Bile↗
PubMed1984

Reversal of the antiproliferative effect of the antiestrogen tamoxifen by polyamines in breast cancer cells.

Numerous studies suggest a relationship between the action of hormones on their target tissues and the synthesis of polyamines. To evaluate the role of polyamines in the mediation of the effect of estrogen on the growth of experimental hormone-responsive mammary cancer, we investigated whether the cytotoxic effect of the antiestrogen tamoxifen could be rescued by exogenous administration of polyamines. When added to N-nitrosomethylurea-induced mammary tumors grown in soft agar in the presence of tamoxifen, putrescine, spermidine, and spermine were able to reverse the inhibitory effect of antiestrogens on colony formation in a dose-dependent fashion. In contrast, no effect on colony number was observed when polyamines were added in the absence of tamoxifen. These results indicate that in this system, the antitumor effect of tamoxifen is mediated through induction of polyamine depletion. Consequently, the data suggest that estrogens may stimulate mitogenesis of the N-nitrosomethylurea-induced mammary tumor through the polyamine pathway.

Animals↗