Deregulation of Polyamines in Cancer Cancer is a major human health problem worldwide and is the second leading cause of death in the United States. Over the past 40 years, significant progress has been made in understanding the molecular basis of cancer , such as serine proteinase, matrix metalloproteinases, cathepsins, and plasminogen activator, which can degrade surrounding tissues Besides all polyamines common in human cells, the group was the first in the world to synthesise their deuterium-labelled counterparts, which are used as internal standards in the analysis, necessary for accurate quantitative polyamine profiling and thus detecting cancer from patients' urine samples
title = Polyamines in cancer, abstract = Polyamines are organic cations shown to control gene expression at the transcriptional, posttranscriptional, and translational levels. Multiple cellular oncogenic pathways are involved in regulation of transcription and translation of polyamine-metabolizing enzymes Learn the 1 Key Nutrient You Need to Stimulate & Boost Body's Immune Cells to Fight Cancer. Rejuvenate & Revitalize Cells With These 8 Ancient Immune Boosting Herbs That Work Polyamines and cancer: Implications for chemoprevention and chemotherapy Shannon L. Nowotarski1, Patrick M. Woster2, and Robert A. Casero Jr.1,* 1Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland 21287 2Department of Drug Discovery and Biomedical Sciences The Medical University of South Carolina Charleston, South Carolina 2942 The amino-acid-derived polyamines have long been associated with cell growth and cancer, and specific oncogenes and tumour-suppressor genes regulate polyamine metabolism. Inhibition of polyamine synthesis has proven to be generally ineffective as an anticancer strategy in clinical trials, but it is a potent cancer chemoprevention strategy in.
Additionally, an expanding number of promising clinical trials with agents targeting polyamines for both therapy and prevention are ongoing. New insights into molecular mechanisms linking dysregulated polyamine catabolism and carcinogenesis suggest additional strategies that can be used for cancer prevention in at-risk individuals Polyamines and prostatic cancer. Schipper RG, Romijn JC, Cuijpers VM, Verhofstad AA. The importance of polyamines in prostatic growth and differentiation has prompted studies to evaluate the clinical relevance of the ornithine decarboxylase/polyamine system in prostatic cancer The amino-acid-derived polyamines have long been associated with cell growth and cancer, and specific oncogenes and tumour-suppressor genes regulate polyamine metabolism. Inhibition of polyamine synthesis has proven to be generally ineffective as an anticancer strategy in clinical trials, but it is a potent cancer chemoprevention strategy in preclinical studies Since polyamines and cancer seem to be intricately linked, it is not surprising at all that the polyamine metabolic pathway has received much attention in cancer drug development. ODC being the rate limiting enzyme in polyamine biosynthesis was the first target in the polyamine pathway The induction of mammary cancer in female Sprague- Dawley rats by a single of 1-methyl-l-nitrosourea was used as an experimental model system for identifying an effective agent in the prevention of breast cancer. The polyamine concentrations in whole mammary gland or mammary epithelial cells remained unchanged in the post-initiatio
Methionine is needed for the production of polyamines (putrescine, spermidine, spermine), which are involved in cellular division and are found in higher concentration in tumors. 11 Polyamines decrease apoptosis, increase proliferation, and are involved in tumorigenesis. 12 Their inhibition has been proposed as a means of reducing cancer risk. 13 Preliminary trials limiting polyamines (through. Increased levels of polyamines, as observed in human cancers, are the result of deregulation of polyamine metabolism and transport (3,4). Consequently, the polyamine biosynthetic, degradative, and transport pathways have been explored as potential targets for both cancer prevention and therapeutic interventions (5-8) urinary polyamines before chemotherapy, exhibited a severalfold increase in the level of polyamine excretion during daunomycin administration, and then entered a remission period in which the polyamines were excreted in normal amounts. Urinary polyamines fell to near normal after surgery 1556 CANCER RESEARCH VOL. 31 Research T1 - Polyamines and cancer. T2 - implications for chemotherapy and chemoprevention. AU - Nowotarski, Shannon L. AU - Woster, Patrick M. AU - Casero, Robert A. PY - 2013. Y1 - 2013. N2 - Polyamines are small organic cations that are essential for normal cell growth and development in eukaryotes The importance of polyamines in prostatic growth and differentiation has prompted studies to evaluate the clinical relevance of the ornithine decarboxylase/polyamine system in prostatic cancer. These studies show that differences in biological behaviour of prostatic (cancer) cells are associated with changes in polyamine levels and/or the activity of their metabolic enzymes. Faulty antizyme.
. Furthermore, and in contrast with all other cell systems in the body, normal and neoplastic cells in the colon are exposed to high. It is the goal of this article to review the latest findings in the field that demonstrate the potential utility of targeting the metabolism and function of polyamines as strategies for both chemotherapy and, possibly more importantly, chemoprevention. Original language. English (US) Pages (from-to) 2937-2953. Number of pages Cancer is a set of diseases characterized by uncontrolled cell growth. In certain cancers of the gastrointestinal tract, the adenomatous polyposis coli (APC) tumor suppressor gene is altered in either germline or somatic cells and causes formation of risk factors, such as benign colonic or intestinal neoplasia, which can progress to invasive cancer
.In a cohort of 50 primary breast tumors, the level of ODC activity demonstrated a strong negative correlation with both disease-free. Polyamines (including putrescine, spermidine, and spermine) are small, cationic molecules that are necessary for cell proliferation and differentiation. Few studies have examined the association of dietary polyamines intake with colorectal cancer risk. The aim of this study was to evaluate total polyamines, putrescine, spermidine, and spermine intake in relation to colorectal cancer risk in China Abstract. Polyamines putrescine, spermidine, and spermine are involved in the growth of breast cancer cells. A possible target of polyamine action is at the site of interaction of transcription factors with their response elements. NF-κB is a member of the rel family of transcription factors that regulate transcription of genes in the.
Studies with transgenic cancer models also support the finding that the effect of MYC on tumor initiation and progression can be attenuated through the repression of polyamine production. High-risk neuroblastomas (an often lethal embryonal tumor in which MYC activation is paramount) deregulate numerous polyamine enzymes to promote the expansion. The study of metabolism has provided remarkable information about the biological basis and therapeutic weaknesses of cancer cells. Classic biochemistry established the importance of metabolic alterations in tumor biology and revealed the importance of various metabolite families to the tumorigenic process. We have evidence of the central role of polyamines, small polycatonic metabolites, in. [Regulation of polyamine and cancer]. by Keijiro Samejima. Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan. Read more related scholarly scientific articles and abstracts Polyamines play an important role in the physiology of neovascularization of tissues; however, their role in angiogenesis also relates to growth, proliferation and migration of cancer cells, which are a suitable model for studying the effects of polyamines on angiogenesis (Takigawa et al., Reference Takigawa, Enomoto, Nishida, Pan, Kinoshita.
Chemoprevention is the long-term use of different chemical agents, both synthetic and natural, to prevent or delay the onset of disease. Since colorectal cancer has a significant environmental component, it is an ideal disease in which to evaluate the potential benefits of chemopreventive agents. The polyamines, spermine, spermidine and putrescine have been involved in almost all the steps of. High concentrations of acetyl polyamines have been observed in human breast cancer compared with the equivalent normal tissue, however, no explanation as to the reason for the increases has been proposed. In this study, we show that changes in the enzymes responsible for the breakdown of acetyl polyamines occur in breast cancer tissue. Spermidine/spermine N 1-acetyltranferase, the first and. Therefore, although polyamines have been classically considered as oncometabolites by its procarcinogenic actions once the tumor is formed, these new studies could indicate that dietary polyamines could be considered for cancer prevention or even for cancer treatment depending on the cancer type in a dose-dependent fashion High dietary polyamines may foster colorectal adenomas. April 14, 2010. Caroline Helwick. Oncology NEWS International, Oncology NEWS International Vol 19 No 4, Volume 19, Issue 4. A high intake of dietary polyamines, which are commonly found in orange juice, corn, red meat, peas, and nuts, has been linked to the size and grade of colorectal. Jänne, J. et al. (1978). Polyamines in Rapid Growth and Cancer, Biochimica et Biophysica Acta. 473:241-293. (APP) Jeffers, L. et al. (1997). Effects of the Polyamine Analogues BE-4-4-4-4, BE-3-7-3, and BE-3-3-3 on the Proliferation of Three Prostate Cancer Cell Lines, Cancer Chemother Pharmacol 40:172-179. (APP
The numerous potential clinical uses of polyamines, their biosynthetic enzymes and enzyme inhibitors, as tumor markers and antitumor agents have been demonstrated in experimental and clinical settings. Gastrointestinal cancers account for a large percentage of cancer deaths in the United States. Colorectal cancer alone is the second most common. OSTI.GOV Journal Article: Polyamines and nonmelanoma skin cancer. Polyamines and nonmelanoma skin cancer. Full Record; Other Related Researc High levels of polyamines were observed and were related to a poor prognosis in cancer patients. However, the mechanism is not obvious. The aim of this study is to mimic the extracellular polyamines in a tumor microenviroment and to explore the role of extracellular polyamines in the proliferation and migration of cancer cells
The major objective of this book is to provide a timely and long lasting guide for investigators in the fields of polyamines, physiology, pharmacology, and cancer research. It will provide a foundation based on research and address the potential for subsequent applications in clinical practice. Polyamine Cell Signaling: Physiology, Pharmacology. The critical role of polyamines in cell growth has led to the development of a number of agents that interfere with polyamine metabolism. These agents are used in cancer therapy. Polyamine analogues upregulate p53 in a cell leading to restriction of proliferation and apoptosis Polyamines and Polyamine Regulators in Prostate Cancer. By David A. Corral, MD The steps to progression for any given tumor are under the control of complex regulatory events, with the overall growth rate determined by the balance of the number of cells undergoing proliferation, cell death, and quiescence Background: Polyamines play a role in cell proliferation and in cancer development: they are mainly carried by red blood cells (RBCs). Abnormally high polyamine levels in RBCs have been demonstrated in patients with various types of cancer and the prognostic value of RBC polyamine levels has also been underlined
In CaCO2 colon cancer cells, the analog causes induction of SSAT, downregulation of ODC, and depletion of cellular polyamines, resulting in cyto-toxicity (33). In addition, SSAT induction appears to be the common event leading to cytotoxicity in non-small-cell lung (SCLC) tumor explants (34) Development of libraries of metabolites characterised with high throughput chromatography-mass spectrometry methods has facilitated the screening of large numbers of metabolites in disease tissue samples. Polyamine metabolism is a new target in pulmonary arterial hypertension also under development in cancer research <https://bit.ly/2YnD17o> Vol. 2. 2 15- 24 1.,\ tic/June' 199 I Cancer Epidemiology, Biomarkers & Prevention 235 Urinary and Erythrocyte Polyamines during the Evaluation of Oral a-Difluoromethylornithine in a Phase I Chemoprevention Clinical Trial
Both polyamines and thrombin modify cancer cells to drive the development of malignant and metastatic tumors. Thrombin is an enzyme in blood plasma that causes the clotting of blood by converting fibrinogen to fibrin. Thrombin is generated as the result of a cascade of coagulation factors. Many of these coagulation factors are increased in. .15%) in serum and acetylputrescine (84.5%), total putrescine (84.0%), N 1. Polyamines are important players in plant growth, stress and disease resistance, but they are also involved in diseases, for example Alzheimer's or infectious diseases. The main research area for the involvement of polyamines in diseases is cancer, as high levels of polyamines are observed in cancer cells. [1
Suitable for investigators in the fields of polyamines, physiology, pharmacology, and cancer research. This book covers various findings relevant to cellular and molecular functions of polyamines. It also provides the underlying conceptual basis and knowledge regarding potential therapeutic targeting polyamines and polyamine metabolism Increase of polyamines within cells resulted in an enhancement of ID1 gene expression. The results of this study reveal details of metabolic pathways that drive epigenetic control of cancer cell stemness and determine effective therapeutic targets in CSCs Polyamines are organic cations shown to control gene expression at the transcriptional, posttranscriptional, and translational levels. Multiple cellular oncogenic pathways are involved in regulation of transcription and translation of polyamine-metabolizing enzymes
cancer cells have limited access to polyamines they enter apoptosis, or controlled cell death. In animal models of cancer, cellular apoptosis can be tracked by measuring tumor weights as well as histological methods. It is known that difluromethylornithine (DFMO), a polyamine synthesis inhibitor, has shown some success in reducing tumor weights Polyamines are naturally occurring compounds essential for cell proliferation and other vital processes. In normal physiological conditions, polyamine concentrations are tightly regulated by balancing production, degradation, import, and export. Because of their roles in cellular growth, polyamines are highly abundant in many cancers
Difluoromethylornithine in Cancer Treatment. Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), has attracted considerable interest initially as a cancer treatment and, more recently, as a preventive agent for cancer, due to its inhibition of the polyamine pathway and cell turnover. Polyamines cause cell. acta oncologica vol. 31, no. 3, pp. 327-331, 1992 urinary polyamines in patients with advanced cervical cancer or pelvic cancer recurrence during and after radiotherapy aldo becciolini, sauro porciani, aldo lanini, riccardo santoni and luca cionin However polyamines stop DFMO from suppressing ODC and therefore cancer cells become more invasive. Polyamines affect the ability of cells to adhere to each other. Because our immune cells need to adhere to cancer cells to recognise them and attack them, failure to do so allows cancer cells to go unrecognised and to develop into tumours Polyamines in Cellular Metabolism, Cancer Biology, Plants and Pathogens. June 22 - 23, 2019 Chairs Nathan K. Sunada and Giulia Baroli Waterville Valley. 56 Packard's Road. Waterville Valley, NH, US. Venue and Travel Information. Conference Description. The 2019 Gordon Research Seminar (GRS) on Polyamines is a unique forum for graduate students. Polyamines are important players in plant growth, stress and disease resistance , but they are also involved in diseases , for example Alzheimer's or infectious diseases. The main research area for the involvement of polyamines in diseases is cancer, as high levels of polyamines are observed in cancer cells
Remaining Mysteries of Molecular Biology: The Role of Polyamines in the Cell. J Mol Biol. 2015 Oct 23;427(21):3389-406. Epub 2015 Jul 5 PubMed. Li J, Meng Y, Wu X, Sun Y. Polyamines and related signaling pathways in cancer. Cancer Cell Int. 2020 Nov 5;20(1):539. PubMed It is thought that cancer's smell may be caused by elevated levels of bad-smelling molecules called polyamines, or by other cancer-specific volatile organic compounds On the Role of Polyamines and Microvesicles in Tumour Development Regulation by Hypoxia and Implications for Therapeutic Intervention of Cancer Johanna Welch Academic Dissertation By due permission of the Faculty of Medicine, Lund University, Sweden, to be publicly defended in GK-salen, BMC, Sölvegatan 19, Lund The risk of a person getting colon cancer in his or her lifetime is about one in 19, according to the American Cancer Society. The Role of Polyamines. For the new study, Raj and colleagues went.
New research uncovers crucial link between polyamines and MYCN. The MYCN oncogene has long been known to be a key cause of a number of deadly solid tumor cancers, including neuroblastoma, which. Histamine, Polyamines, and Cancer Miguel A´ ngel Medina,* Ana Rodrı´guez Quesada, Ignacio Nu´n˜ez de Castro and Francisca Sa´nchez-Jime´nez DEPARTAMENTO DE BIOQUı´MICA Y BIOLOGı´A MOLECULAR,FACULTAD DE CIENCIAS,UNIVERSIDAD DE MA´ LAGA, E-29071 MA´ LAGA,SPAIN ABSTRACT
The polyamines putrescine, spermidine, and spermine are small, aliphatic amines that play an important role in multiple cellular functions. Activation of the polyamine pathway is involved in carcinogenesis and other aspects of tumor biology including in breast cancer. Levels of ornithine decarboxylase (ODC), the first and rate-limiting enzyme. ORLANDO -- Dietary polyamines may represent a modifiable risk factor for colon cancer, according to a new analysis of data from a prevention trial presented here. High intake of polyamine-rich. Polyamine Depletion. Polyamines are found in every cell in the body and are required for cell growth and division. Excessive production of polyamines is used by cancer cells to suppress detection and attack by the immune system. Polyamines contribute to an increase of myeloid-derived suppressor cells (MDSCs) in tumor microenvironments
As polyamines are tightly correlated with regulation of cellular growth, there has been an increasing effort over the past years to link polyamine metabolism to cancer. Increased polyamine levels are coupled with increased cell proliferation, decreased apoptosis and increased expression of genes associated with tumor invasion and metastasis. POLYAMINES Polyamines are organic cations formed by the enzymatic decarboxylation of ornithine to yield putrescine and by further additions from decarboxylated S-adenosyl methionine to form spermidine and spermine. Ornithine decarboxylase and polyamine content are increased in many carcinomas including skin and colon cancer Polyamines work at least in part by regulating specific gene expression Reference: E.W. Gerner and F.L. Meyskens. Polyamines and cancer: old molecules, new understanding. Nature reviews Cancer 4: 781-792, 2004. INTERMEDIARY METABOLISM - SUGGESTED READING R.W. Ruddon and R.W. Kufe, In Holland-Frei Cancer Medicine - 8th Ed, Part II, Section 1, 9 Loser C, Folsch UR, Paprotny C et al (1990) Polyamines in colorectal cancer. Evaluation of polyamine concentrations in the colon tissue, serum, and urine of 50 patients with colorectal cancer. Cancer 65(4):958-966 PubMed CrossRef Google Schola [CANCER RESEARCH 37, 939-942, March 1977] Meeting Report Conference on Polyamines in Cancer In 1971, Russell (10) reported high levels of polyamines in the urine of cancer patients. This investigation was begun as part of a search for biochemical markers useful in the diagnosis of cancer and in following the course of therapy (12)
3. Polyamines and their role in DNA condensation to nano-particles 4. Amine oxidases and their utilization in nanomedicine 5. Cell killing by polyamines and BSAO 6. Hyperthermia in combination with polyamine metabolites in therapeutic applications 7. Nanoparticle delivery of BSAO in cancer cells 8. Conclusions and future perspectives 1. . Altomare and Phanstiel are creating a combination treatment of two inhibitor drugs. The first blocks the factory inside the cell where polyamines are made. The second locks the door or pathway that tumor cells use to import polyamines
Polyamines T A Smith Annual Review of Plant Physiology 1,4-Diaminobutane (Putrescine), Spermidine, and Spermine C W Tabor, and and H Tabor Annual Review of Biochemistry Do Polyamines Have Roles in Plant Development? P T Evans, and and R L Malmber Polyamines in Colorectal Cancer Evaluation of Polyamine Concentrations in the Colon Tissue, Serum, and Urine of 50 Patients With Colorectal Cancer CHRISTIAN LOSER, MD, ULRICH R. FOLSCH, MD, CHRISTOPH PAPROTNY, MD, AND WERNER CREUTZFELDT, MD Total, free, and acetylated polyamine concentrations were measured simultaneously in colon tissue, serum,. The importance of polyamines in prostatic growth and differentiation has prompted studies to evaluate the clinical relevance of the ornithine decarboxylase/polyamine system in prostatic cancer. These studies show that differences in biological behaviour of prostatic (cancer) cells are associated with changes in polyamine levels and/or the. Breast cancer is a complex heterogeneous disease with multiple underlying causes. The polyamines putrescine, spermidine, and spermine are polycationic molecules essential for cell proliferation. Their biosynthesis is upregulated in breast cancer and they contribute to disease progression An adenovirus carrying antisense ODC (rAd-ODC/Ex3as) was infected to prostate cancer cells PC-3 and LNCap. Expression of ODC and concentration of polyamines in cells were determined by Western.
In colon cancer, the activities of polyamine-synthesizing enzymes and polyamine content are increased 3-4-fold compared to the equivalent normal colonic mucosa, and polyamines have even been attributed as markers of neoplastic proliferation in the colon . However, the exact mechanisms on the role of internal polyamine pool affecting GI mucosal. This finding suggests that polyamines may be critically involved in the development of breast cancer metastasis. We have, indeed, observed that administration of DFMO markedly reduced in vitro invasiveness of the hormone-independent MDA-MB-435 and MDA-MB-231 human breast cancer cell lines
Dietary Polyamines Intake and Risk of Colorectal Cancer: A Case-Control Study by Chu-Yi Huang, Nutrients 2020, 12(11), 3575; Polyamines (including putrescine, spermidine, and spermine) are small, cationic molecules that are necessary for cell proliferation and differentiation Polyamines and prostatic cancer. Biochem Soc Trans 2003;31:375-380. Crossref, Medline, Google Scholar; 9 Takyi EE, Fuller DJ, Donaldson LJ, Thomas GH. Deoxyribonucleic acid and polyamine synthesis in rat ventral prostrate: effects of age of the intact rat and androgen stimulation of the castrated rat with testosterone, 5 alpha.
Adding complexity, there is a possible direct interaction between the thioredoxin system and polyamines. In MCF-7 human breast cancer cells, transfected Trx-1 decreased the expression and enzyme activity of spermidine/spermine N1-acetyltransferase and also lowered putrescine levels without changing those of spermine or spermidine 2020 Gastric Cancer Summit at StanfordPresenter: Keith Wilson, MD | Vanderbilt Universit The Polyamines GRC is the ultimate meeting in this field and the conference will cover a wide range of topics in basic, translational and clinical research. This GRC is attended by biologists, chemists, structural biologists and clinicians, and investigators from academia, biotech and pharmaceutical sectors Polyamines are such ancient, ubiquitous molecules that bacteria apparently can even use those produced by their animal hosts. Thus, biofilms may promote cancer in the colon by inducing chronic inflammation and associated cell proliferation. That increased cell proliferation would be accompanied by a rise in the production of polyamines
The role of polyamines in longevity and disease is discussed. A link between polyamine contents and cancer progression is reported, as is the use of polyamine metabolites as diagnostic markers in the initial stages of cancer. Moreover, a novel approach that utilizes the polyamine pathway of a parasite as a drug target in African sleeping. The aim of the work was the investigation of the influence of polyamines on formation of nuclear transcription factor kappa B (NF-kB) complex with specific DNA-sequences nuclear response elements (NRE), and the study of content of p50 and p65 (NF-kB subunits) in breast tumor cells under polyamines metabolism modulation Antioxidant capacity of polyamines was compared using two commonly used antioxidant capacity assays. The inhibitory effect of polyamines on cancer cell growth was investigated using murine breast cancer 4T1 cells and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay to monitor cell growth
However, 1,3-diaminopropane, putrescine, spermine and N-acetylspermidine levels in serum increased in breast cancer patients. These four serum polyamines may be a good index to study both production and metabolism of polyamines, and a useful tool in assessment of the polyamine status of breast cancer patients Recently, we have shown that ornithine decarboxylase (ODC), a rate-controlling enzyme in the polyamine biosynthetic pathway, is overexpressed in prostate cancer (PCA) and prostatic fluid in humans (R. R. Mohan et al., Clin. Cancer Res., 5: 143-147 Background: Prostate cancer is a major health issue, and prevention of prostate cancer and/or its progression will yield benefits for men. Difluoromethylornithine (DFMO) is an antiproliferative agent, inhibiting ornithine decarboxylase, the first enzyme in the polyamine pathway, and has been studied as a therapeutic and chemopreventive agent. The prostate has high levels of tissue polyamines. Polyamines are essential for tumor cell growth, and the polyamine pathway represents an attractive target for cancer treatment. Several polyamine transport proteins have been cloned and characterized in bacteria and yeast cells; however, the mechanism of polyamine entry into mammalian cells remains poorly defined, although a role for proteoglycans has been suggested