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1.  Anti-Tumor Effects of Novel 5-O-Acyl Plumbagins Based on the Inhibition of Mammalian DNA Replicative Polymerase Activity 
PLoS ONE  2014;9(2):e88736.
We previously found that vitamin K3 (menadione, 2-methyl-1,4-naphthoquinone) inhibits the activity of human mitochondrial DNA polymerase γ (pol γ). In this study, we focused on plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), and chemically synthesized novel plumbagins conjugated with C2:0 to C22:6 fatty acids (5-O-acyl plumbagins). These chemically modified plumbagins enhanced mammalian pol inhibition and their cytotoxic activity. Plumbagin conjugated with chains consisting of more than C18-unsaturated fatty acids strongly inhibited the activities of calf pol α and human pol γ. Plumbagin conjugated with oleic acid (C18:1-acyl plumbagin) showed the strongest suppression of human colon carcinoma (HCT116) cell proliferation among the ten synthesized 5-O-acyl plumbagins. The inhibitory activity on pol α, a DNA replicative pol, by these compounds showed high correlation with their cancer cell proliferation suppressive activity. C18:1-Acyl plumbagin selectively inhibited the activities of mammalian pol species, but did not influence the activities of other pols and DNA metabolic enzymes tested. This compound inhibited the proliferation of various human cancer cell lines, and was the cytotoxic inhibitor showing strongest inhibition towards HT-29 colon cancer cells (LD50 = 2.9 µM) among the nine cell lines tested. In an in vivo anti-tumor assay conducted on nude mice bearing solid tumors of HT-29 cells, C18:1-acyl plumbagin was shown to be a promising tumor suppressor. These data indicate that novel 5-O-acyl plumbagins act as anti-cancer agents based on mammalian DNA replicative pol α inhibition. Moreover, the results suggest that acylation of plumbagin is an effective chemical modification to improve the anti-cancer activity of vitamin K3 derivatives, such as plumbagin.
doi:10.1371/journal.pone.0088736
PMCID: PMC3919815  PMID: 24520419
2.  Overexpression, crystallization and preliminary X-­ray diffraction analysis of l-ribose isomerase from Acinetobacter sp. strain DL-28 
Recombinant l-ribose isomerase from Acinetobacter sp. was crystallized. Diffraction data were collected to 2.2 Å resolution.
Acinetobacter sp. l-ribose isomerase (l-RI) catalyzes a reversible isomerization reaction between l-ribose and l-ribulose. To date, information on l-RI remains limited and its amino-acid sequence shows no similarity to those of any known enzymes. Here, recombinant His-tagged l-RI was successfully overexpressed, purified and crystallized. Crystals of His-tagged l-RI were obtained by the hanging-drop vapour-diffusion method at room temperature as two crystal forms which belonged to the monoclinic space group C2, with unit-cell parameters a = 96.60, b = 105.89, c = 71.83 Å, β = 118.16°, and the orthorhombic space group F222, with unit-cell parameters a = 96.44, b = 106.26, c = 117.83 Å. Diffraction data were collected to 3.1 and 2.2 Å resolution, respectively.
doi:10.1107/S1744309111030351
PMCID: PMC3212383  PMID: 22102048
l-ribose isomerase; rare sugars; Acinetobacter sp.
3.  Structure of l-rhamnose isomerase in complex with l-rhamnopyranose demonstrates the sugar-ring opening mechanism and the role of a substrate sub-binding site☆ 
FEBS Open Bio  2012;3:35-40.
l-Rhamnose isomerase (l-RhI) catalyzes the reversible isomerization of l-rhamnose to l-rhamnulose. Previously determined X-ray structures of l-RhI showed a hydride-shift mechanism for the isomerization of substrates in a linear form, but the mechanism for opening of the sugar-ring is still unclear. To elucidate this mechanism, we determined X-ray structures of a mutant l-RhI in complex with l-rhamnopyranose and d-allopyranose. Results suggest that a catalytic water molecule, which acts as an acid/base catalyst in the isomerization reaction, is likely to be involved in pyranose-ring opening, and that a newly found substrate sub-binding site in the vicinity of the catalytic site may recognize different anomers of substrates.
Highlights:
▸ l-Rhamnose isomerase catalyzes the reversible isomerization of l-rhamnose to l-rhamnulose. ▸ The catalytic reaction includes opening of the sugar-ring, but the mechanism is unclear. ▸ The structure of the enzyme with substrates in a pyranose ring form was determined. ▸ A catalytic water molecule is probably involved in opening the pyranose ring. ▸ A newly found substrate sub-binding site recognizes the anomers of substrates.
doi:10.1016/j.fob.2012.11.008
PMCID: PMC3668531  PMID: 23772372
l-Rhamnose isomerase; Pseudomonas stutzeri; Sugar-ring opening mechanism; Rare sugar; X-ray structure; l-RhI, l-rhamnose isomerase; E. coli, Escherichia coli; P. stutzeri, Pseudomonas stutzeri; D327N, mutant P. stutzeril-RhI, with a substitution of Asp327 with Asn; H101N, mutant P. stutzeril-RhI, with a substitution of H101 with Asn; RNS, l-rhamnose in a linear form; β-RPS, β-l-rhamnopyranose; α-RPS, α-l-rhamnopyranose; α-APS, α-d-allopyranose
4.  Oral administration of monogalactosyl diacylglycerol from spinach inhibits colon tumor growth in mice 
Previously, we observed that purified monogalactosyl diacylglycerol (MGDG), a major glycoglycerolipid from spinach, selectively inhibits the activities of mammalian replicative DNA polymerases (α, δ and ε). However, the function of MGDG following ingestion is not well-known. In the present study, spinach MGDG suppressed the proliferation of Colon26 mouse colon cancer cells with an LD50 of 24 μg/ml in vitro. γ-cyclodextrin (CD)-MGDG complex was prepared and administered orally following Colon26 mouse tumor adhesion for 26 days. It was observed that 20 mg/kg equivalent (eq.) of the CD-MGDG complex reduced tumor volume by ∼60% compared with that of the vehicle-treated controls. In immunohistochemical analysis, the CD-MGDG complex group showed a decreased number of proliferating cell nuclear antigen (PCNA)-positive cells and reduction of mitosis in the tumor cells compared with the control group. In addition, the CD-MGDG complex increased the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive apoptotic cells and inhibited CD31-positive tumor blood vessel growth significantly. These results suggest that MGDG has the potential for cancer prevention and health promotion.
doi:10.3892/etm.2012.792
PMCID: PMC3524182  PMID: 23251235
monogalactosyl diacylglycerol; γ-cyclodextrin; DNA polymerase; antitumor; anti-proliferation
5.  Crystallization and preliminary X-ray analysis of AAMS amidohydrolase, the final enzyme in degradation pathway I of pyridoxine 
Recombinant α-(N-acetylaminomethylene)succinic acid amidohydrolase from M. loti MAFF303099 was crystallized and diffraction data were collected at 2.7 Å resolution.
α-(N-Acetylaminomethylene)succinic acid (AAMS) amidohydrolase from Mesorhizobium loti MAFF303099, which is involved in a degradation pathway of vitamin B6 and catalyzes the degradation of AAMS to acetic acid, ammonia, carbon dioxide and succinic semialdehyde, has been overexpressed in Escherichia coli. To elucidate the reaction mechanism based on the tertiary structure, the recombinant enzyme was purified and crystallized by the sitting-drop vapour-diffusion method using PEG 8000 as precipitant. A crystal of the enzyme belonged to the monoclinic space group C2, with unit-cell parameters a = 393.2, b = 58.3, c = 98.9 Å, β = 103.4°, and diffraction data were collected to 2.7 Å resolution. The V M value and calculation of the self-rotation function suggested that three dimers with a threefold symmetry were possibly present in the asymmetric unit.
doi:10.1107/S1744309109026864
PMCID: PMC2720345  PMID: 19652351
α-(N-acetylaminomethylene)succinic acid amidohydrolase; Mesorhizobium loti; pyridoxine-degradation pathway
6.  Inhibitory Effects of Glycyrrhetinic Acid on DNA Polymerase and Inflammatory Activities 
We investigated the inhibitory effect of three glycyrrhizin derivatives, such as Glycyrrhizin (compound 1), dipotassium glycyrrhizate (compound 2) and glycyrrhetinic acid (compound 3), on the activity of mammalian pols. Among these derivatives, compound 3 was the strongest inhibitor of mammalian pols α, β, κ, and λ, which belong to the B, A, Y, and X families of pols, respectively, whereas compounds 1 and 2 showed moderate inhibition. Among the these derivatives tested, compound 3 displayed strongest suppression of the production of tumor necrosis factor-α (TNF-α) induced by lipopolysaccharide (LPS) in a cell-culture system using mouse macrophages RAW264.7 and peritoneal macrophages derived from mice. Moreover, compound 3 was found to inhibit the action of nuclear factor-κB (NF-κB) in engineered human embryonic kidney (HEK) 293 cells. In addition, compound 3 caused greater reduction of 12-O-tetradecanoylphorbol-13-acetate-(TPA-) induced acute inflammation in mouse ear than compounds 1 and 2. In conclusion, this study has identified compound 3, which is the aglycone of compounds 1 and 2, as a promising anti-inflammatory candidate based on mammalian pol inhibition.
doi:10.1155/2012/650514
PMCID: PMC3138047  PMID: 21785649
7.  Crystallization and preliminary X-ray diffraction analysis of a protease-resistant mutant form of human galectin-8 
A protease-resistant mutant form of human galectin-8 has been crystallized and diffraction data have been collected to 3.4 Å resolution.
A crystal of a protease-resistant mutant form of human galectin-8, a tandem-repeat-type galectin with two carbohydrate-recognition domains, was obtained using the hanging-drop method and was found to belong to the tetragonal space group P43212, with unit-cell parameters a = 78.93, b = 78.93, c = 132.05 Å. Diffraction data were collected to a resolution of 3.4 Å.
doi:10.1107/S1744309109013554
PMCID: PMC2675598  PMID: 19407390
galectin-8; carbohydrate-recognition domains; tandem-repeat-type galectins
8.  Variation in Fatty Acid Distribution of Different Acyl Lipids in Rice (Oryza sativa L.) Brans 
Nutrients  2011;3(4):505-514.
The lipids extracted from rice brans were classified by thin-layer chromatography into eight fractions, and their fatty acid (FA) compositions were investigated among five different Japanese cultivars. The lipids of these rice brans comprised mainly triacylglycerols (TAG; 84.9-86.0 wt%), free FA (4.2-4.6 wt%), and phospholipids (PL; 6.5-6.7 wt%), whilst other components were also detected in minor proportions (0.2-2.1 wt%). The PL components included phosphatidyl choline (43.3-46.8 wt%) phosphatidyl ethanolamine (25.0-27.3 wt%) and phosphatidyl inositol (20.2-23.2 wt%). Comparison of the different cultivars showed, with a few exceptions, no substantial difference (P > 0.05) in FA distribution. FA distribution of TAG among the five cultivars was characterized as: unsaturated FA predominantly concentrated at the sn-2 position and saturated FA primarily occupying the sn-1 or sn-3 position in these lipids. These results suggest that the rice bran lipids may be well incorporated into our daily diet to improve nutritional value of the Japanese diet.
doi:10.3390/nu3040505
PMCID: PMC3257686  PMID: 22254108
different acyl lipids; fatty acid distributions; phospholipids; rice bran lipids; triacylglycerols
9.  Effects of Intermediates between Vitamins K2 and K3 on Mammalian DNA Polymerase Inhibition and Anti-Inflammatory Activity 
Previously, we reported that vitamin K3 (VK3), but not VK1 or VK2 (=MK-4), inhibits the activity of human DNA polymerase γ (pol γ). In this study, we chemically synthesized three intermediate compounds between VK2 and VK3, namely MK-3, MK-2 and MK-1, and investigated the inhibitory effects of all five compounds on the activity of mammalian pols. Among these compounds, MK-2 was the strongest inhibitor of mammalian pols α, κ and λ, which belong to the B, Y and X families of pols, respectively; whereas VK3 was the strongest inhibitor of human pol γ, an A-family pol. MK-2 potently inhibited the activity of all animal species of pol tested, and its inhibitory effect on pol λ activity was the strongest with an IC50 value of 24.6 μM. However, MK-2 did not affect the activity of plant or prokaryotic pols, or that of other DNA metabolic enzymes such as primase of pol α, RNA polymerase, polynucleotide kinase or deoxyribonuclease I. Because we previously found a positive relationship between pol λ inhibition and anti-inflammatory action, we examined whether these compounds could inhibit inflammatory responses. Among the five compounds tested, MK-2 caused the greatest reduction in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced acute inflammation in mouse ear. In addition, in a cell culture system using mouse macrophages, MK-2 displayed the strongest suppression of the production of tumor necrosis factor (TNF)-α induced by lipopolysaccharide (LPS). Moreover, MK-2 was found to inhibit the action of nuclear factor (NF)-κB. In an in vivo mouse model of LPS-evoked acute inflammation, intraperitoneal injection of MK-2 in mice led to suppression of TNF-α production in serum. In conclusion, this study has identified VK2 and VK3 intermediates, such as MK-2, that are promising anti-inflammatory candidates.
doi:10.3390/ijms12021115
PMCID: PMC3083694  PMID: 21541047
vitamin K; MK-2; DNA polymerase λ; enzyme inhibitor; anti-inflammation
10.  Overexpression, purification, crystallization and preliminary X-ray crystal analysis of Bacillus pallidus d-arabinose isomerase 
Recombinant B. pallidus d-arabinose isomerase was crystallized and diffraction data were collected to 2.3 Å resolution.
d-Arabinose isomerase catalyzes the isomerization of d-arabinose to d-ribulose. Bacillus pallidus d-arabinose isomerase has broad substrate specificity and can catalyze the isomerization of d-arabinose, l-fucose, l-xylose, l-galactose and d-­altrose. Recombinant B. pallidus d-arabinose isomerase was overexpressed, purified and crystallized. A crystal of the enzyme was obtained by the sitting-drop method at room temperature and belonged to the orthorhombic space group P21212, with unit-cell parameters a = 144.9, b = 127.9, c = 109.5 Å. Diffraction data were collected to 2.3 Å resolution.
doi:10.1107/S1744309108028352
PMCID: PMC2564884  PMID: 18931442
d-arabinose isomerase; l-fucose isomerase; Bacillus pallidus
11.  Structure of a putative molybdenum-cofactor biosynthesis protein C (MoaC) from Sulfolobus tokodaii (ST0472) 
The crystal structure of a putative molybdenum-cofactor biosynthesis protein C (MoaC) from S. tokodaii (ST0472) was determined at 2.2 Å resolution.
The crystal structure of a putative molybdenum-cofactor (Moco) biosynthesis protein C (MoaC) from Sulfolobus tokodaii (ST0472) was determined at 2.2 Å resolution. The crystal belongs to the monoclinic space group C2, with unit-cell parameters a = 123.31, b = 78.58, c = 112.67 Å, β = 118.1°. The structure was solved by molecular replacement using the structure of Escherichia coli MoaC as the probe model. The asymmetric unit is composed of a hexamer arranged as a trimer of dimers with noncrystallographic 32 symmetry. The structure of ST0472 is very similar to that of E. coli MoaC; however, in the ST0472 protein an additional loop formed by the insertion of seven residues participates in intermonomer interactions and the new structure also reveals the formation of an interdimer β-sheet. These features may contribute to the stability of the oligomeric state.
doi:10.1107/S174430910801590X
PMCID: PMC2443982  PMID: 18607082
molybdenum cofactors; Moco-biosynthesis protein; Sulfolobus tokodaii
12.  Regiospecific Profiles of Fatty Acids in Triacylglycerols and Phospholipids from Adzuki Beans (Vigna angularis) 
Nutrients  2010;2(1):49-59.
Regiospecific distributions of fatty acids (FA) of triacylglycerols (TAG) and phospholipids (PL) isolated from five cultivars of adzuki beans (Vigna angularis) were investigated. The lipids comprised mainly PL (72.2-73.4 wt-%) and TAG (20.6-21.9 wt-%), whilst other components were detected in minor proportions (0.1-3.4 wt-%). The principal profiles of the FA distribution in the TAG and PL were evident in the beans among the five cultivars: unsaturated FA were predominantly distributed in the sn-2 position, whilst saturated FA primarily occupied the sn-1 or the sn-3 position in the these lipids. The results would be useful information to both producers and consumers for manufacturing traditional adzuki confectionaries such as wagashi in Japan.
doi:10.3390/nu20100049
PMCID: PMC3257609  PMID: 22253991
adzuki beans (Vigna angularis); fatty acids; phosphatidylcholine; phosphatidyl- ethanolamine; phosphatidylinositol; regiospecific characteristics; triacylglycerols
13.  The relationship between the molecular structure of natural acetogenins and their inhibitory activities which affect DNA polymerase, DNA topoisomerase and human cancer cell growth 
Acetogenins from the Annonaceous plant are a fatty acid-derived natural product. Chemically synthesized natural acetogenins, such as mucocin (compound 1), jimenezin (compound 2), muconin (compound 4), pyranicin (compound 5) and pyragonicin (compound 6) were investigated. Concomitantly, 19-epi jimenezin (compound 3), 10-epi pyragonicin (compound 7) and a γ-lactone (compound 8), which is estimated to be a biosynthetic precursor of acetogenins, were synthesized and investigated. Compounds 5 and 6 strongly inhibited, and compound 7 moderately inhibited the activities of mammalian DNA polymerases (pols), such as replicative pol α and repair/recombination-related pol β and λ, and also inhibited human DNA topoisomerase (topos) I and II activities. On the other hand, compounds 1–4 and 8 did not influence the activities of any pols and topos. Compound 5 was the strongest inhibitor of the pols and topos tested, and the IC50 values were 5.0–9.6 μM, respectively. These compounds also suppressed human cancer cell growth with almost the same tendency as the inhibition of pols and topos. Compound 5 was the strongest suppressor of the proliferation of the promyelocytic leukemia cell line, HL-60, in human cancer cell lines tested with an LD50 value of 9.4 μM, and arrested the cells at G1 phases, indicating that it blocks DNA replication by inhibiting the activity of pols rather than topos. This compound also induced cell apoptosis. The relationship between the three-dimensional molecular structure of acetogenins and these inhibitory activities is discussed. The results suggested that compound 5 is a lead compound of potentially useful cancer chemotherapy agents.
doi:10.3892/etm_00000004
PMCID: PMC3490394  PMID: 23136587
acetogenins; pyranicin; enzyme inhibitor; DNA polymerase; DNA topoisomerase; cell cycle arrest; apoptosis; anti-cancer agent; computer simulation
14.  3-O-Methylfunicone, a Selective Inhibitor of Mammalian Y-Family DNA Polymerases from an Australian Sea Salt Fungal Strain 
Marine Drugs  2009;7(4):624-639.
We isolated a pol inhibitor from the cultured mycelia extract of a fungal strain isolated from natural salt from a sea salt pan in Australia, which was identified as 3-O-methylfunicone by spectroscopic analyses. This compound selectively inhibited the activities of mammalian Y-family DNA polymerases (pols) (i.e., pols η, ι and κ). Among these pols, human pol κ activity was most strongly inhibited, with an IC50 value of 12.5 μM. On the other hand, the compound barely influenced the activities of the other families of mammalian pols, such as A-family (i.e., pol γ), B-family (i.e., pols α, δ and ɛ) or X-family (i.e., pols β, λ and terminal deoxynucleotidyl transferase), and showed no effect on the activities of fish pol δ, plant pols, prokaryotic pols and other DNA metabolic enzymes, such as calf primase of pol α, human immunodeficiency virus type-1 (HIV-1) reverse transcriptase, human telomerase, T7 RNA polymerase, mouse IMP dehydrogenase (type II), human topoisomerases I and II, T4 polynucleotide kinase or bovine deoxyribonuclease I. This compound also suppressed the growth of two cultured human cancer cell lines, HCT116 (colon carcinoma cells) and HeLa (cervix carcinoma cells), and UV-treated HeLa cells exhibited lower clonogenic survival in the presence of inhibitor.
doi:10.3390/md7040624
PMCID: PMC2810227  PMID: 20098603
3-O-methylfunicone; Y-family DNA polymerase; DNA polymerase κ; enzyme inhibitor; marine fungal strains; Australian sea salt; anti-cancer drug
15.  Purification, crystallization and preliminary X-ray diffraction studies of d-tagatose 3-epimerase from Pseudomonas cichorii  
Recombinant d-tagatose 3-epimerase from P. cichorii was purified and crystallized. Diffraction data were collected to 2.5 Å resolution.
d-Tagatose 3-epimerase (D-TE) from Pseudomonas cichorii catalyzes the epimerization of various ketohexoses at the C3 position. The epimerization of d-­psicose has not been reported with epimerases other than P. cichorii D-­TE and d-psicose 3-epimerase from Agrobacterium tumefaciens. Recombinant P. cichorii D-TE has been purified and crystallized. Crystals of P. cichorii D-TE were obtained by the sitting-drop method at room temperature. The crystal belongs to the monoclinic space group P21, with unit-cell parameters a = 76.80, b = 94.92, c = 91.73 Å, β = 102.82°. Diffraction data were collected to 2.5 Å resolution. The asymmetric unit is expected to contain four molecules.
doi:10.1107/S1744309107001169
PMCID: PMC2330126  PMID: 17277456
d-tagatose 3-epimerase; rare sugars; Pseudomonas cichorii
16.  β-d-Altrose 
The mol­ecule of the title compound, C6H12O6, [systematic name: (2R,3S,4R,5R,6R)-6-(hydroxy­meth­yl)oxane-2,3,4,5-tetrol] adopts a 4 C 1 chair conformation with the anomeric hydroxyl group in the equatorial position. All hydroxyl groups act as donors and acceptors in hydrogen bonding and the mol­ecule is involved in ten inter­molecular O—H⋯O inter­actions [O⋯O = 2.672 (5)–2.776 (4) Å] with eight neighbouring mol­ecules. Two independent O—H⋯O—H⋯ helices extending along the z axis are found in this structure.
doi:10.1107/S1600536809000397
PMCID: PMC2968302  PMID: 21581893
17.  Crystallization and preliminary X-ray diffraction studies of l-rhamnose isomerase from Pseudomonas stutzeri  
Recombinant l-rhamnose isomerase from P. stutzeri has been crystallized. Diffraction data have been collected to 2.0 Å resolution.
l-Rhamnose isomerase from Pseudomonas stutzeri (P. stutzeri l-RhI) catalyzes not only the reversible isomerization of l-rhamnose to l-rhamnulose, but also isomerization between various rare aldoses and ketoses. Purified His-tagged P. stutzeri l-RhI was crystallized by the hanging-drop vapour-diffusion method. The crystals belong to the monoclinic space group P21, with unit-cell parameters a = 74.3, b = 104.0, c = 107.0 Å, β = 106.8°. Diffraction data have been collected to 2.0 Å resolution. The molecular weight of the purified P. stutzeri l-RhI with a His tag at the C-terminus was confirmed to be 47.7 kDa by MALDI–TOF mass-spectrometric analysis and the asymmetric unit is expected to contain four molecules.
doi:10.1107/S174430910601596X
PMCID: PMC2243077  PMID: 16754978
l-rhamnose isomerase; rare sugars; Pseudomonas stutzeri
18.  Mechanism of Growth Inhibition of Human Cancer Cells by Conjugated Eicosapentaenoic Acid, an Inhibitor of DNA Polymerase and Topoisomerase 
DNA topoisomerases (topos) and DNA polymerases (pols) are involved in many aspects of DNA metabolism such as replication reactions. We found that long chain unsaturated fatty acids such as polyunsaturated fatty acids (PUFA) (i.e., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) inhibited the activities of eukaryotic pols and topos in vitro, and the inhibitory effect of conjugated fatty acids converted from EPA and DHA (cEPA and cDHA) on pols and topos was stronger than that of normal EPA and DHA. cEPA and cDHA did not affect the activities of plant and prokaryotic pols or other DNA metabolic enzymes tested. cEPA was a stronger inhibitor than cDHA with IC50 values for mammalian pols and human topos of 11.0 – 31.8 and 0.5 – 2.5 μM, respectively. cEPA inhibited the proliferation of two human leukemia cell lines, NALM-6, which is a p53-wild type, and HL-60, which is a p53-null mutant, and the inhibitory effect was stronger than that of normal EPA. In both cell lines, cEPA arrested in the G1 phase, and increased cyclin E protein levels, indicating that it blocks the primary step of in vivo DNA replication by inhibiting the activity of replicative pols rather than topos. DNA replication-related proteins, such as RPA70, ATR and phosphorylated-Chk1/2, were increased by cEPA treatment in the cell lines, suggesting that cEPA led to DNA replication fork stress inhibiting the activities of pols and topos, and the ATR-dependent DNA damage response pathway could respond to the inhibitor of DNA replication. The compound induced cell apoptosis through both p53-dependent and p53-independent pathways in cell lines NALM-6 and HL-60, respectively. These results suggested the therapeutic potential of conjugated PUFA, such as cEPA, as a leading anti-cancer compound that inhibited pols and topos activities.
PMCID: PMC3871801
conjugated eicosapentaenoic acid (cEPA); DNA polymerase; DNA topoisomerase; enzyme inhibitor; DNA replication; cell proliferation; cell cycle arrest; p53; apoptosis

Results 1-18 (18)