The inhibitory action of fatty acids on DNA polymerase β

Mizushina, Yoshiyuki; Yoshida, Shonen; Matsukage, Akio; Sakaguchi, Kengo

doi:10.1016/s0304-4165(97)00067-6

Cited by 187 publications

(240 citation statements)

References 23 publications

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“…Activities of DNA polymerases were measured by the methods described previously. 24,25) The substrates of DNA polymerases used were poly(dA)/oligo(dT) [12][13][14][15][16][17][18] and dTTP as template-primer DNA and nucleotide substrate, respectively. One unit of each DNA polymerase activity was defined as the amount of enzyme that catalyzes the incorporation of 1 nmol of deoxyribonucleotide triphosphate (i.e., dTTP) into the synthetic template-primers (i.e., poly(dA)/oligo(dT) [12][13][14][15][16][17][18] , A/T=2/1) in 60 min at 37°C under the normal reaction conditions for each of the enzymes.…”

Section: Methodsmentioning

confidence: 99%

A novel DNA topoisomerase inhibitor: dehydroebriconic acid, one of the lanostane‐type triterpene acids from Poria cocos

et al. 2004

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Traditional Chinese medicinal plants are a treasure house for screening novel inhibitors of DNA polymerases and DNA topoisomerases from mammals; in the present study, nine lanostanetype triterpene acids were found in sclerotium of Poria cocos. Among the nine compounds, only dehydroebriconic acid could potently inhibit DNA topoisomerase II (topo II) activity (IC50=4.6 μM), while the compound moderately inhibited the activities of DNA polymerases α, β, γ, δ, ɛ, η, iota;, κ and λ only from mammals, to similar extents. Another compound, dehydrotrametenonic acid, also showed moderate inhibitory effects against topo II (IC50=37.5 μM) and weak effects against all the polymerases tested. Both compounds showed no inhibitory effect against topo I, higher plant (cauliflower) DNA polymerase I (α‐like polymerase) or II (βlike polymerase), calf thymus terminal deoxynucleotidyl transferase, human immunodeficiency virus type‐1 reverse transcriptase, prokaryotic DNA polymerases such as the Klenow fragment of E. coli DNA polymerase I, Taq DNA polymerase and T4 DNA polymerase, or DNA metabolic enzymes such as T7 RNA polymerase, T4 polynucleotide kinase and bovine deoxyribonu‐clease I. These findings suggest that dehydroebriconic acid and dehydrotrametenonic acid should be designated as topo II‐preferential inhibitors, although they also moderately inhibited all the mammalian DNA polymerases tested. Both dehydrotrametenonic acid and dehydroebriconic acid could prevent the growth of human gastric cancer cells, and their LD50 values were 63.6 and 38.4 μM, respectively. The cells were halted at the G1 phase in the cell cycle. The relation between the structure of triterpene acids and their inhibitory activities is discussed.

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Section: Methodsmentioning

confidence: 99%

A novel DNA topoisomerase inhibitor: dehydroebriconic acid, one of the lanostane‐type triterpene acids from Poria cocos

et al. 2004

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“…The reaction mixtures for these pols have been described previously (Myobatake et al, 2012;Mizushina et al, 1996;Mizushina et al, 1997 (Mizushina et al, 1996;Mizushina et al, 1997).…”

Section: Measurement Of Inhibitory Activities Of Pols and Other Dna Mmentioning

confidence: 99%

Screening of Mammalian DNA Polymerase Inhibitors from Rosemary Leaves and Analysis of the Anti-inflammatory and Antiallergic Effects of the Isolated Compounds

Mizushina

Onodera

Kuriyama

et al. 2014

FSTR

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In this study, on screening mammalian DNA polymerase (pol) inhibitors from the extracts of 20 edible plants, we found that leaves of rosemary (Rosmarinus officinalis L.) showed the strongest pol inhibition; furthermore, we isolated four components, carnosic acid, carnosol, ursolic acid, and rosmarinic acid, from an extract of the leaves.Carnosic acid inhibited the activities of all 11 mammalian pols tested. In descending order of their inhibitory effect on pol λ, which is a DNA repair/recombination pol, the four compounds ranked as follows: carnosic acid > ursolic acid > carnosol > rosmarinic acid. The inhibition of pol λ by these compounds was significantly correlated with both in vivo anti-inflammatory and antiallergic effects, including on 12-O-tetradecanoylphorbol-13-acetate-induced inflammatory mouse ear edema, and immunoglobulin E-induced passive cutaneous anaphylactic reaction in mice.These results indicate that rosemary and its constituent, carnosic acid, are potential therapeutic food candidates for inflammatory and allergic diseases.

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“…The reaction mixtures for calf pol α, rat pol β, plant pol α and prokaryotic pols were described previously 21,22 . The reaction mixtures for human pol γ, and human pols δ and ε were previously described by Umeda et al 12 and Ogawa et al 23 , respectively.…”

Section: Dna Polymerase Assaysmentioning

confidence: 99%

“…Activity in the absence of inhibitor was considered 100 activity, and the remaining activity at each inhibitor concentration was determined relative to this value. One unit of pol activity was defi ned as the amount of enzyme that catalyzed the incorporation of 1 nmol dNTP dTTP into synthetic DNA template-primers in 60 min at 37 under normal reaction conditions for each enzyme 21,22 .…”

Section: Dna Polymerase Assaysmentioning

confidence: 99%

.BETA.-Sitosteryl (6'-O-linoleoyl)-glucoside of Soybean (Glycine max L.) Crude Extract Inhibits Y-Family DNA Polymerases

et al. 2010

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The inhibitory action of fatty acids on DNA polymerase β

Cited by 187 publications

References 23 publications

A novel DNA topoisomerase inhibitor: dehydroebriconic acid, one of the lanostane‐type triterpene acids from Poria cocos

A novel DNA topoisomerase inhibitor: dehydroebriconic acid, one of the lanostane‐type triterpene acids from Poria cocos

Screening of Mammalian DNA Polymerase Inhibitors from Rosemary Leaves and Analysis of the Anti-inflammatory and Antiallergic Effects of the Isolated Compounds

.BETA.-Sitosteryl (6'-O-linoleoyl)-glucoside of Soybean (Glycine max L.) Crude Extract Inhibits Y-Family DNA Polymerases

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