Antitumor activity of the polyamine analog N1,N11-diethylnorspermine against human prostate carcinoma cells

Schipper, Raymond G.; Deli, Geertu; Deloyer, Patricia; Lange, W.; Schalken, Jack A.; Verhofstad, A.A.J.

doi:10.1002/1097-0045(20000901)44:4<313::aid-pros8>3.0.co;2-d

Cited by 36 publications

(25 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since the polyamine uptake inhibitors tested so far have been relatively toxic (for review, see [5,14,15]), there is a need for a less toxic compound that ideally would inhibit both ODC and the polyamine transporter simultaneously. Agmatine appears to be such a compound, since it has been proven to exhibit virtually low systemic toxicity [16,17,18], to reduce ODC activity [19,20], and to inhibit polyamine uptake as well [20,21,22].…”

Section: Introductionmentioning

confidence: 55%

Pharmacological characteristics of the specific transporter for the endogenous cell growth inhibitor agmatine in six tumor cell lines

Heinen

Brüss

Bönisch

et al. 2003

Int J Colorectal Dis

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 55%

Pharmacological characteristics of the specific transporter for the endogenous cell growth inhibitor agmatine in six tumor cell lines

Heinen

Brüss

Bönisch

et al. 2003

Int J Colorectal Dis

View full text Add to dashboard Cite

“…The polyamine pools were similar to those described above for the prostate cell lines. In another study using four human prostate cell lines (PC-3, TSU-pr1, Du-145, and JCA-1), treatment with 100 µM DENSPM for 48 h resulted in putrescine, spermidine and spermine pools of between 1 and 3 nmol/mg of protein [20]. Thus, despite the very high DENSPM concentration used in this study, polyamine levels were not much lower than in cells treated with 10 µM DENSPM.…”

Section: Effect Of Denspm Treatment On Polyamine Poolsmentioning

confidence: 99%

Inhibition of cell proliferation and induction of apoptosis by N1,N11-diethylnorspermine-induced polyamine pool reduction

Oredsson

Alm

Dahlberg

et al. 2007

Biochemical Society Transactions

View full text Add to dashboard Cite

Reduction of cellular polyamine pools results in inhibition of cell proliferation and sometimes in induction of cell death. Reduction of cellular polyamine pools can be achieved by several strategies involving all the mechanisms of polyamine homoeostasis, i.e. biosynthesis, catabolism and transport across the cell membrane. In the present paper, we concentrate on results achieved using the polyamine analogue DENSPM (N(1),N(11)-diethylnorspermine) on different cell lines. We discuss polyamine levels in DENSPM-treated cells in relation to effects on cell cycle kinetics and induction of apoptosis. To really understand the role of polyamines in cell cycle regulation and apoptosis, we believe it is now time to go through the vast polyamine literature in a meta-analysis-based manner. This short review does not claim to be such a study, but it is our hope to stimulate such studies in the polyamine field. Such work is especially important from the viewpoint of introducing drugs that affect polyamine homoeostasis in the treatment of various diseases such as cancer.

show abstract

“…Furthermore, it also reduces ODC and SAMdc activities (58,90). These joined effects lead to polyamine depletion (87,91). To simulate the effects of DENSPM in our model, we assumed that this unmetabolizable analog causes its effect by a modulation of synthesis and degradation constants for those enzymes ruled by the Schimke equation.…”

Section: Simulations Of Changes Of Acetyl-coa Availability Predict Thmentioning

confidence: 99%

Mathematical Modeling of Polyamine Metabolism in Mammals

Rodríguez‐Caso

Montañez

Cascante

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

Polyamines are considered as essential compounds in living cells, since they are involved in cell proliferation, transcription, and translation processes. Furthermore, polyamine homeostasis is necessary to cell survival, and its deregulation is involved in relevant processes, such as cancer and neurodegenerative disorders. Great efforts have been made to elucidate the nature of polyamine homeostasis, giving rise to relevant information concerning the behavior of the different components of polyamine metabolism, and a great amount of information has been generated. However, a complex regulation at transcriptional, translational, and metabolic levels as well as the strong relationship between polyamines and essential cell processes make it difficult to discriminate the role of polyamine regulation itself from the whole cell response when an experimental approach is given in vivo. To overcome this limitation, a bottom-up approach to model mathematically metabolic pathways could allow us to elucidate the systemic behavior from individual kinetic and molecular properties. In this paper, we propose a mathematical model of polyamine metabolism from kinetic constants and both metabolite and enzyme levels extracted from bibliographic sources. This model captures the tendencies observed in transgenic mice for the so-called key enzymes of polyamine metabolism, ornithine decarboxylase, S-adenosylmethionine decarboxylase and spermine spermidine N-acetyl transferase. Furthermore, the model shows a relevant role of S-adenosylmethionine and acetyl-CoA availability in polyamine homeostasis, which are not usually considered in systemic experimental studies.During much of the last century, biology was an attempt to reduce biological phenomena to the behavior of molecules. Despite the enormous success of this approach, most biological functions arise from interactions among many components, yielding nonlinear behavior that has been fine tuned by natural selection to achieve specific functional properties (1, 2). Therefore, a comprehensive understanding of biological functions requires a new systemic perspective. In the last few years, systems biology and synthetic biology have emerged to fulfill this goal (3-5). Systems biology approaches are hypothesis-driven and involve iterative rounds of model building, prediction, experimentation, and model refinement and development (6, 7). Computer science development is allowing faster and faster numerical simulations of mathematical models. Interesting and relevant mathematical models of several well known metabolic pathways have been published very recently (8 -10). Far from replacing knowledge acquisition from experimental evidence, mathematical modeling allows to test and define more accurately hypothesis that have to be experimentally tested later. Furthermore, modeling allows to build a comprehensive framework based on a compilation of the experimental data provided by the scientific community. With this philosophy, we propose and study a mathematical model of polyamine metabolism. We...

show abstract

Antitumor activity of the polyamine analog N1,N11-diethylnorspermine against human prostate carcinoma cells

Cited by 36 publications

References 21 publications

Pharmacological characteristics of the specific transporter for the endogenous cell growth inhibitor agmatine in six tumor cell lines

Pharmacological characteristics of the specific transporter for the endogenous cell growth inhibitor agmatine in six tumor cell lines

Inhibition of cell proliferation and induction of apoptosis by N1,N11-diethylnorspermine-induced polyamine pool reduction

Mathematical Modeling of Polyamine Metabolism in Mammals

Contact Info

Product

Resources

About