• Title/Summary/Keyword: Polyamine metabolites

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Polyamines and Their Metabolites as Diagnostic Markers of Human Diseases

  • Park, Myung Hee;Igarashi, Kazuei
    • Biomolecules & Therapeutics
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    • v.21 no.1
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    • pp.1-9
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    • 2013
  • Polyamines, putrescine, spermidine and spermine, are ubiquitous in living cells and are essential for eukaryotic cell growth. These polycations interact with negatively charged molecules such as DNA, RNA, acidic proteins and phospholipids and modulate various cellular functions including macromolecular synthesis. Dysregulation of the polyamine pathway leads to pathological conditions including cancer, inflammation, stroke, renal failure and diabetes. Increase in polyamines and polyamine synthesis enzymes is often associated with tumor growth, and urinary and plasma contents of polyamines and their metabolites have been investigated as diagnostic markers for cancers. Of these, diacetylated derivatives of spermidine and spermine are elevated in the urine of cancer patients and present potential markers for early detection. Enhanced catabolism of cellular polyamines by polyamine oxidases (PAO), spermine oxidase (SMO) or acetylpolyamine oxidase (AcPAO), increases cellular oxidative stress and generates hydrogen peroxide and a reactive toxic metabolite, acrolein, which covalently incorporates into lysine residues of cellular proteins. Levels of protein-conjuagated acrolein (PC-Acro) and polyamine oxidizing enzymes were increased in the locus of brain infarction and in plasma in a mouse model of stroke and also in the plasma of stroke patients. When the combined measurements of PC-Acro, interleukin 6 (IL-6), and C-reactive protein (CRP) were evaluated, even silent brain infarction (SBI) was detected with high sensitivity and specificity. Considering that there are no reliable biochemical markers for early stage of stroke, PC-Acro and PAOs present promising markers. Thus the polyamine metabolites in plasma or urine provide useful tools in early diagnosis of cancer and stroke.

Testing of Cancer Chemopreventive Potential of Prunella vulgaris L. Aqua-acupuncture Solution Using Biochemical Markers of Carcinogenesis (발암과정 생화학적 표식자를 이용한 하고초 약침액의 암예방 활성 측정)

  • Park, Sin-Hwa;Cho, Kyoung-Hee;Shon, Yun-Hee;Lim, Jong-Kook;Nam, Kyung-Soo
    • Korean Journal of Pharmacognosy
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    • v.32 no.2 s.125
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    • pp.163-167
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    • 2001
  • Prunella vulgaris L. aqua-acupuncture solution (PVAS) was tested for cancer chemopreventive activity using chemoprevention-associated biochemical end points. The following effects were measured. : (a) inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-induced cytochrome P4501A1 activity (b) inhibition of $[^3H]B[a]P-DNA$ binding (c) inhibition of phorbol 12-myristate 13-acetate (TPA)-induced free radical formation in HL-60 cells (d) inhibition of polyamine metabolism. PVAS inhibited cytochrome P4501A1-mediated ethoxyresorufin-O-deethylase activity. The binding of $[^3H]B[a]P$ metabolites to DNA of NCTC-clone 1469 cells was inhibited significantly by PVAS. There is 22% inhibition of TPA-induced free radical formation in human leukemic cells with 5 mg/ml PVAS. Proliferation of Acanthamoeba castellanii was inhibited by PAVS at concentration of 30 mg/ml. PAVS positive in these assays may inhibit the carcinogenesis process and is considered very promising cancer-preventing agent because of its multiple activities.

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