The old and new biochemistry of polyamines

Polyamines are ubiquitous positively charged amines found in all organisms. These molecules play a crucial role in many biological functions including cell growth, gene regulation and differentiation. The three major polyamines produced in all mammalian cells are putrescine, spermidine and spermine....

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Published inBiochimica et biophysica acta. General subjects Vol. 1862; no. 9; pp. 2053 - 2068
Main Authors Bae, Dong-Hun, Lane, Darius J.R., Jansson, Patric J., Richardson, Des R.
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 01.09.2018
Subjects
Acireductone dioxygenase 1 (ADI1)
Animals
antineoplastic agents
biosynthesis
cell growth
Cell Proliferation
chelating agents
enzymes
genes
Humans
Iron
mammals
methionine
neoplasm cells
neoplasms
Neoplasms - physiopathology
Ornithine decarboxylase
patients
Polyamines
Polyamines - metabolism
prognosis
putrescine
S-adenosylmethionine (AdoMet)
spermidine
Spermidine/spermine-N1-acetyltransferase 1 (SAT1)
spermine
transporters
MAT
Spermidine/spermine-N1-acetyltransferase 1 (SAT1)
SMOX
AMD1
SLC3A2
Iron
Ornithine decarboxylase
Polyamines
OAZ1
SAT1
AZIN1
S-adenosylmethionine (AdoMet)
ODC
AdoMet
SRM
Acireductone dioxygenase 1 (ADI1)
SLC22A16
ADI1
SMS
DFMO
PAOX
Spermidine/spermine-N-acetyltransferase 1 (SAT1)
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Abstract Polyamines are ubiquitous positively charged amines found in all organisms. These molecules play a crucial role in many biological functions including cell growth, gene regulation and differentiation. The three major polyamines produced in all mammalian cells are putrescine, spermidine and spermine. The intracellular levels of these polyamines depend on the interplay of the biosynthetic and catabolic enzymes of the polyamine and methionine salvage pathway, as well as the involvement of polyamine transporters. Polyamine levels are observed to be high in cancer cells, which contributes to malignant transformation, cell proliferation and poor patient prognosis. Considering the critical roles of polyamines in cancer cell proliferation, numerous anti-polyaminergic compounds have been developed as anti-tumor agents, which seek to suppress polyamine levels by specifically inhibiting polyamine biosynthesis, activating polyamine catabolism, or blocking polyamine transporters. However, in terms of the development of effective anti-cancer therapeutics targeting the polyamine system, these efforts have unfortunately resulted in little success. Recently, several studies using the iron chelators, O-trensox and ICL670A (Deferasirox), have demonstrated a decline in both iron and polyamine levels. Since iron levels are also high in cancer cells, and like polyamines, are required for proliferation, these latter findings suggest a biochemically integrated link between iron and polyamine metabolism. •Polyamines are ubiquitous positively charged amines found in all organisms.•Polyamines play a crucial role in many biological functions.•Polyamine levels are high in cancer cells and are a therapeutic target.•Several iron chelators have been shown to reduce polyamine levels.•There is a biochemically integrated link between iron and polyamine metabolism.
AbstractList Polyamines are ubiquitous positively charged amines found in all organisms. These molecules play a crucial role in many biological functions including cell growth, gene regulation and differentiation. The three major polyamines produced in all mammalian cells are putrescine, spermidine and spermine. The intracellular levels of these polyamines depend on the interplay of the biosynthetic and catabolic enzymes of the polyamine and methionine salvage pathway, as well as the involvement of polyamine transporters. Polyamine levels are observed to be high in cancer cells, which contributes to malignant transformation, cell proliferation and poor patient prognosis. Considering the critical roles of polyamines in cancer cell proliferation, numerous anti-polyaminergic compounds have been developed as anti-tumor agents, which seek to suppress polyamine levels by specifically inhibiting polyamine biosynthesis, activating polyamine catabolism, or blocking polyamine transporters. However, in terms of the development of effective anti-cancer therapeutics targeting the polyamine system, these efforts have unfortunately resulted in little success. Recently, several studies using the iron chelators, O-trensox and ICL670A (Deferasirox), have demonstrated a decline in both iron and polyamine levels. Since iron levels are also high in cancer cells, and like polyamines, are required for proliferation, these latter findings suggest a biochemically integrated link between iron and polyamine metabolism.
Polyamines are ubiquitous positively charged amines found in all organisms. These molecules play a crucial role in many biological functions including cell growth, gene regulation and differentiation. The three major polyamines produced in all mammalian cells are putrescine, spermidine and spermine. The intracellular levels of these polyamines depend on the interplay of the biosynthetic and catabolic enzymes of the polyamine and methionine salvage pathway, as well as the involvement of polyamine transporters. Polyamine levels are observed to be high in cancer cells, which contributes to malignant transformation, cell proliferation and poor patient prognosis. Considering the critical roles of polyamines in cancer cell proliferation, numerous anti-polyaminergic compounds have been developed as anti-tumor agents, which seek to suppress polyamine levels by specifically inhibiting polyamine biosynthesis, activating polyamine catabolism, or blocking polyamine transporters. However, in terms of the development of effective anti-cancer therapeutics targeting the polyamine system, these efforts have unfortunately resulted in little success. Recently, several studies using the iron chelators, O-trensox and ICL670A (Deferasirox), have demonstrated a decline in both iron and polyamine levels. Since iron levels are also high in cancer cells, and like polyamines, are required for proliferation, these latter findings suggest a biochemically integrated link between iron and polyamine metabolism. •Polyamines are ubiquitous positively charged amines found in all organisms.•Polyamines play a crucial role in many biological functions.•Polyamine levels are high in cancer cells and are a therapeutic target.•Several iron chelators have been shown to reduce polyamine levels.•There is a biochemically integrated link between iron and polyamine metabolism.
Polyamines are ubiquitous positively charged amines found in all organisms. These molecules play a crucial role in many biological functions including cell growth, gene regulation and differentiation. The three major polyamines produced in all mammalian cells are putrescine, spermidine and spermine. The intracellular levels of these polyamines depend on the interplay of the biosynthetic and catabolic enzymes of the polyamine and methionine salvage pathway, as well as the involvement of polyamine transporters. Polyamine levels are observed to be high in cancer cells, which contributes to malignant transformation, cell proliferation and poor patient prognosis. Considering the critical roles of polyamines in cancer cell proliferation, numerous anti-polyaminergic compounds have been developed as anti-tumor agents, which seek to suppress polyamine levels by specifically inhibiting polyamine biosynthesis, activating polyamine catabolism, or blocking polyamine transporters. However, in terms of the development of effective anti-cancer therapeutics targeting the polyamine system, these efforts have unfortunately resulted in little success. Recently, several studies using the iron chelators, O-trensox and ICL670A (Deferasirox), have demonstrated a decline in both iron and polyamine levels. Since iron levels are also high in cancer cells, and like polyamines, are required for proliferation, these latter findings suggest a biochemically integrated link between iron and polyamine metabolism.Polyamines are ubiquitous positively charged amines found in all organisms. These molecules play a crucial role in many biological functions including cell growth, gene regulation and differentiation. The three major polyamines produced in all mammalian cells are putrescine, spermidine and spermine. The intracellular levels of these polyamines depend on the interplay of the biosynthetic and catabolic enzymes of the polyamine and methionine salvage pathway, as well as the involvement of polyamine transporters. Polyamine levels are observed to be high in cancer cells, which contributes to malignant transformation, cell proliferation and poor patient prognosis. Considering the critical roles of polyamines in cancer cell proliferation, numerous anti-polyaminergic compounds have been developed as anti-tumor agents, which seek to suppress polyamine levels by specifically inhibiting polyamine biosynthesis, activating polyamine catabolism, or blocking polyamine transporters. However, in terms of the development of effective anti-cancer therapeutics targeting the polyamine system, these efforts have unfortunately resulted in little success. Recently, several studies using the iron chelators, O-trensox and ICL670A (Deferasirox), have demonstrated a decline in both iron and polyamine levels. Since iron levels are also high in cancer cells, and like polyamines, are required for proliferation, these latter findings suggest a biochemically integrated link between iron and polyamine metabolism.
Author Bae, Dong-Hun
Lane, Darius J.R.
Jansson, Patric J.
Richardson, Des R.
Author_xml – sequence: 1
  givenname: Dong-Hun
  surname: Bae
  fullname: Bae, Dong-Hun
  organization: Molecular Pharmacology and Pathology Program, Department of Pathology and Bosch Institute, The Medical Foundation Building (K25), University of Sydney, Sydney, New South Wales 2006, Australia
– sequence: 2
  givenname: Darius J.R.
  surname: Lane
  fullname: Lane, Darius J.R.
  email: darius.lane@florey.edu.au
  organization: Melbourne Dementia Research Centre, The Florey Institute of Neuroscience and Mental Health, Kenneth Myer Building, The University of Melbourne, Parkville, Victoria 3052, Australia
– sequence: 3
  givenname: Patric J.
  surname: Jansson
  fullname: Jansson, Patric J.
  organization: Molecular Pharmacology and Pathology Program, Department of Pathology and Bosch Institute, The Medical Foundation Building (K25), University of Sydney, Sydney, New South Wales 2006, Australia
– sequence: 4
  givenname: Des R.
  surname: Richardson
  fullname: Richardson, Des R.
  email: d.richardson@med.usyd.edu.au
  organization: Molecular Pharmacology and Pathology Program, Department of Pathology and Bosch Institute, The Medical Foundation Building (K25), University of Sydney, Sydney, New South Wales 2006, Australia
BackLink https://www.ncbi.nlm.nih.gov/pubmed/29890242$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
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Spermidine/spermine-N1-acetyltransferase 1 (SAT1)
SMOX
AMD1
SLC3A2
Iron
Ornithine decarboxylase
Polyamines
OAZ1
SAT1
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SRM
Acireductone dioxygenase 1 (ADI1)
SLC22A16
ADI1
SMS
DFMO
PAOX
Spermidine/spermine-N-acetyltransferase 1 (SAT1)
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Snippet Polyamines are ubiquitous positively charged amines found in all organisms. These molecules play a crucial role in many biological functions including cell...
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SubjectTerms Acireductone dioxygenase 1 (ADI1)
Animals
antineoplastic agents
biosynthesis
cell growth
Cell Proliferation
chelating agents
enzymes
genes
Humans
Iron
mammals
methionine
neoplasm cells
neoplasms
Neoplasms - physiopathology
Ornithine decarboxylase
patients
Polyamines
Polyamines - metabolism
prognosis
putrescine
S-adenosylmethionine (AdoMet)
spermidine
Spermidine/spermine-N1-acetyltransferase 1 (SAT1)
spermine
transporters
Title The old and new biochemistry of polyamines
URI https://dx.doi.org/10.1016/j.bbagen.2018.06.004
https://www.ncbi.nlm.nih.gov/pubmed/29890242
https://www.proquest.com/docview/2054933377
https://www.proquest.com/docview/2131848879
Volume 1862
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