The role of polyamines in gastric cancer

McNamara, Kara M.; Gobert, Alain P.; Wilson, Keith T.

doi:10.1038/s41388-021-01862-x

Cited by 29 publications

(20 citation statements)

References 105 publications

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“…The Aa is one of the most well studied compounds in most fruits and vegetables, including tomatoes, and the content is known to correlate negatively with maturation in tomato [23], which justifies the analysis of its content in the present study. Here, the Aa content of the tomatoes was analyzed according to Bergquist et al [49] with some modifications.…”

Section: Ascorbic Acid (Aa) Analysissupporting

confidence: 52%

“…In contrast to these positive effects, PAs have been suggested to have procarcinogenic properties in cancer patients, since polyamine concentrations caused by enhanced biosynthesis have been found in several cancers [16,[18][19][20][21]. In cancer diagnosed patients, consumption of PAs increased the risk of cancer cell proliferation [22,23] or increased the malignant cell growth rate in established tumors [22]. The connection between PAs and cancer therapy and treatments has resulted in an increased interest in understanding how the polyamine metabolism can be of use in anticancer strategies [24].…”

Section: Introductionmentioning

confidence: 99%

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Genotype and Maturity Stage Affect the Content and Composition of Polyamines in Tomato—Possible Relations to Plant and Human Health

et al. 2021

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Polyamines (PAs) are molecules affecting several physiological characteristics in all living organisms with cell protective effects, thereby impacting plant and human health. Here, we used HPLC-DAD-ESI-MS to evaluate the content and composition of PAs in eight tomato genotypes over their maturation period, and related the content and composition to other quality traits and possible implications for plant and human health. The tomato genotype, maturity stage and their interactions, significantly affected the content and composition of PAs. Two of the genotypes, ‘Huichol’ and ‘Rio Grande’ showed consistently lower levels of PAs than the other evaluated genotypes. The variation in content and composition of PAs among genotypes was found to vary inconsistently over the maturation period. Putrescine content in the different genotypes either did not vary significantly, increased, or showed the lowest level in the middle of the maturation period, while spermidine content decreased or did not show significant variation. The genotypes ‘HT36′ and ‘HT25′ showed high levels of PAs during red and green maturity stages, respectively, and can thereby be seen as suitable health promoting red and green candidate tomatoes. Depiction of variation of the PAs creates opportunities for breeding and production of health promoting tomato as a food or food additive.

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Section: Ascorbic Acid (Aa) Analysissupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Genotype and Maturity Stage Affect the Content and Composition of Polyamines in Tomato—Possible Relations to Plant and Human Health

et al. 2021

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“…Polyamines are ubiquitous and play critical roles in a variety of key processes, including growth, differentiation and macromolecular synthesis. Because of their relevance in rapidly proliferating cells, they have long been of interest in cancer and parasite research [ 32 , 33 , 38 , 39 , 40 , 41 , 42 ]. Furthermore, polyamines have shown protective properties, including anti-oxidant, anti-aging, and cardio- and neuroprotective functions [ 42 , 43 , 44 , 45 , 46 ].…”

Section: Significance Of Polyaminesmentioning

confidence: 99%

Polyamine Metabolism in Leishmania Parasites: A Promising Therapeutic Target

Carter¹,

Kawasaki²,

Nahata³

et al. 2022

Medical Sciences

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Parasites of the genus Leishmania cause a variety of devastating and often fatal diseases in humans and domestic animals worldwide. The need for new therapeutic strategies is urgent because no vaccine is available, and treatment options are limited due to a lack of specificity and the emergence of drug resistance. Polyamines are metabolites that play a central role in rapidly proliferating cells, and recent studies have highlighted their critical nature in Leishmania. Numerous studies using a variety of inhibitors as well as gene deletion mutants have elucidated the pathway and routes of transport, revealing unique aspects of polyamine metabolism in Leishmania parasites. These studies have also shed light on the significance of polyamines for parasite proliferation, infectivity, and host–parasite interactions. This comprehensive review article focuses on the main polyamine biosynthetic enzymes: ornithine decarboxylase, S-adenosylmethionine decarboxylase, and spermidine synthase, and it emphasizes recent discoveries that advance these enzymes as potential therapeutic targets against Leishmania parasites.

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“…This is subsequently hydroxylated by deoxyhypusine hydroxylase (DOHH) to form hypusinated eIF5A. In vivo, proteolysis of hypusinated eIF5A releases hypusine, i.e., N ε -(4-amino-2hydroxybutyl)lysine (not shown) implicated in various human pathological conditions including infectious diseases, diabetes, neurodevelopment disorders and cancer (Nakanishi and Cleveland 2016;McNamara et al 2021;Park et al 2021). The two-step biosynthesis of hypusine is illustrated in Scheme 1.…”

Section: Introductionmentioning

confidence: 99%

“…Hypusination is required for the activity of eIF5A, mammalian cell proliferation, and neurodevelopment. eIF5A has been implicated in various human pathological conditions including infectious diseases, diabetes, neurodevelopment disorders and cancer (Nakanishi and Cleveland 2016 ; McNamara et al 2021 ; Park et al 2021 ). The two-step biosynthesis of hypusine is illustrated in Scheme 1 .…”

Section: Introductionmentioning

confidence: 99%

Specific and sensitive GC–MS analysis of hypusine, Nε-(4-amino-2-hydroxybutyl)lysine, a biomarker of hypusinated eukaryotic initiation factor eIF5A, and its application to the bi-ethnic ASOS study

et al. 2022

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Hypusination is a unique two-step enzymatic post-translational modification of the Nε-amino group of lysine-50 of the eukaryotic initiation factor 5A (eIF5A). We developed a specific and sensitive gas chromatography–mass spectrometry (GC–MS) method for the measurement of biological hypusine (Hyp), i.e., Nε-(4-amino-2-hydroxybutyl)lysine. The method includes a two-step derivatization of Hyp: first esterification with 2 M HCl in CH3OH (60 min, 80 °C) to the methyl ester (Me) and then acylation with penta-fluoro-propionic (PFP) anhydride in ethyl acetate (30 min, 65 °C). Esterification with 2 M HCl in CD3OD was used to prepare the internal standard. The major derivatization product was identified as the un-labelled (d0Me) and the deuterium-labelled methyl esters (d3Me) derivatives: d0Me-Hyp-(PFP)5 and d3Me-Hyp-(PFP)5, respectively. Negative-ion chemical ionization generated the most intense ions with m/z 811 for d0Me-Hyp-(PFP)5 and m/z 814 for the internal standard d3Me-Hyp-(PFP)5. Selected-ion monitoring of m/z 811 and m/z 814 was used in quantitative analyses. Free Hyp was found in spot urine samples (10 µL) of two healthy subjects at 0.60 µM (0.29 µmol Hyp/mmol creatinine) in the female and 1.80 µM (0.19 µmol Hyp/mmol creatinine) in the male subject. The mean accuracy of the method in these urine samples spiked with 1–5 µM Hyp was 91–94%. The limit of detection (LOD) of the method is 1.4 fmol Hyp. The method was applied to measure the urinary excretion rates of Hyp in healthy black (n = 38, age 7.8 ± 0.7 years) and white (n = 41, age 7.7 ± 1.0 years) boys of the Arterial Stiffness in Offspring Study (ASOS). The Hyp concentrations were 3.55 [2.68–5.31] µM (range 0.54–9.84 µM) in the black boys and 3.87 [2.95–5.06] µM (range 1.0–11.7 µM) in the white boys (P = 0.64). The creatinine-corrected excretion rates were 0.25 [0.20–0.29] µmol/mmol (range 0.11–0.36 µmol/mmol) in the black boys and 0.26 [0.21–0.30] µmol/mmol (range 0.10–0.45 µmol/mmol) in the white boys (P = 0.82). These results suggest that there is no ethnic-related difference in the ASOS population in the eIF5A modification. Remarkable differences were found between black and white boys with respect to correlations of urinary Hyp with amino acids and advanced glycation end-products of Lys, Arg and Cys. Deoxyhypusine, formally the direct precursor of Hyp, seems not to be excreted in the urine by healthy subjects.

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The role of polyamines in gastric cancer

Cited by 29 publications

References 105 publications

Genotype and Maturity Stage Affect the Content and Composition of Polyamines in Tomato—Possible Relations to Plant and Human Health

Genotype and Maturity Stage Affect the Content and Composition of Polyamines in Tomato—Possible Relations to Plant and Human Health

Polyamine Metabolism in Leishmania Parasites: A Promising Therapeutic Target

Specific and sensitive GC–MS analysis of hypusine, Nε-(4-amino-2-hydroxybutyl)lysine, a biomarker of hypusinated eukaryotic initiation factor eIF5A, and its application to the bi-ethnic ASOS study

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