Selective toxicity of glycyrrhetinic acid against tumorigenic r/m HM-SFME-1 cells is potentially attributed to downregulation of glutathione.

Natural products from plants are expected to play significant roles in creating new, safe and improved chemopreventive and therapeutic antitumor agents. Selectivity is also an important issue in cancer prevention and therapy. The present study was designed to extend our previous study on the c-Ha-ras and c-myc-induced tumor cell-selective antiproliferative effects of a licorice component, glycyrrhetinic acid (GA). An in silico ligand-receptor docking simulation revealed that GA acts as an 11ß-hydroxysteroid dehydrogenase type 2 inhibitor. GA disrupted the redox balance in tumor cells through upregulation of reactive oxygen species and downregulation of glutathione (GSH). The GA-induced GSH reduction and cytotoxicity were enhanced by an inhibitor of GSH, l-buthionine-[S,R]-sulfoximine. N-acetyl-l-cysteine, an antioxidant and precursor of GSH, restored the GA-induced GSH reduction and cytotoxicity in tumor cells. Taken together, these data highlighting the downregulation of GSH by GA and the efficacy of GSH in ameliorating GA-mediated cytotoxicity support the notion that GSH is involved in the selective toxicity of GA toward tumor cells.

Control of the magnetoelectric domain-wall stability by a magnetic field in a multiferroic MnWO4.

The relation between the orientation of the magnetic field and the flopped ferroelectric polarization has been investigated for multiferroic MnWO4. The ferroelectric single-domain state is retained across the polarization flop process when the direction of the applied magnetic field slightly deviates from the b axis within the ab plane. Furthermore, the electric polarization in the high-field P parallela phase is reversed when the P parallelb-to-P parallela transition takes place while decreasing and increasing the magnetic fields oppositely canted from the b axis. These results indicate that the symmetry breaking induced by a canted magnetic field determines the direction of the polarization flop, which corresponds to the direction of the vector spin chirality. The stability of the magnetoelectric domain walls in a canted magnetic field play a key role in the directional control of the electric polarization flop phenomenon.

Effects of Maillard reaction products on the oxidative cleavage and polymerization of protein under ascorbic acid-transition metal system.

This study investigated the effects of Maillard reaction products (MRPs) on the oxidative cleavage and polymerization of BSA (bovine serum albumin) in an aqueous system. In L-ascorbic acid (AsA) and Cu(II) or Fe(III) reaction system, 50-60% of BSA was cleaved under physiological conditions (37 degrees C, pH 7.2). The oxidative cleavage induced by AsA-Cu(II) system was suppressed to the extent of 32-86% by model melanoidins or brown pigments from amino acids and foodstuffs. In the AsA-Fe(III) system, the oxidative cleavage was inhibited to the extent of 45-93% by melanoidins and brown pigments. However, this cleavage was promoted by amino acid Amadori rearrangement products and brown pigment from soy paste. Therefore, MRPs show both suppression and promotion activity on oxidative cleavage of BSA in the system of AsA and a transition metal. The quantity of Amadori rearrangement moiety (ARM) in melanoidins from Lysine and brown pigments molecules from foods was also measured. From these data, it was estimated that the suppression and/or promotion of oxidative cleavage of BSA did not only depend on the quantity of ARM, but also depended on the chemical structure of ARM in melanoidins or brown pigments.

Digestibility and peptide patterns of modified lysozyme after hydrolyzing by protease.

In this study, lysozyme was modified by glucose in the dry state (50 degrees C, RH 75%) and the peptide patterns were investigated using HPLC after hydrolyzing by the pepsin-pancreatin system. Native or modified lysozyme was also administered to rats to clarify digestibility and absorbability in vivo. The digestibility of lysozyme modified by glucose decreased depending on reaction time. In vitro, when lysine residue of lysozyme was modified by glucose at a level of about 50%, the generated peptide patterns with molecular weights (MW) below 3,000 Da were similar to that of native lysozyme, and the yields of peptides from modified lysozyme were lower than those of native lysozyme. However, there are some differences between the hydrolysate patterns of native and modified lysozymes of MW over 10,000 Da, and the yields of these peptides from modified lysozyme are higher than those from native lysozyme. In vivo, the percentage of 30 d-modified lysozyme remaining in rat digestive tracts after 90 min of administration was 11% of the dosage as compared with 0.4% for native lysozyme. However, the digestive peptide patterns of native or modified lysozymes in the rat small intestine were also similar to those of the control. Consequently, it is estimated that modified lysozyme was digested as easily as native lysozyme when the degree of modification of lysine residue by glucose was about 60% even in vivo.

Antioxidative properties of products from amino acids or peptides in the reaction with glucose.

The livers of rats fed with a brownish "soybean paste" (Miso) or peptides-glucose reaction mixture showed lower TBA and chemiluminescence values than those of the control. From these results, it was clear that Miso and peptide-glucose reaction products also exhibited antioxidative effect in vivo. In order to explain this mechanism, the scavenging activity against reactive oxygen species (ROS) of various Maillard reaction products (MRPs) were studied. It was confirmed that peptide-glucose reaction products. Amadori rearrangement products, melanoidins, modified protein and its hydrolysate, brown pigments isolated from Miso and other foodstuffs showed strong scavenging activity against hydroxyl radical and superoxide anion. Consequently, it was estimated that scavenging activity of MRPs against ROS played an important role in the antioxidative effect of MRPs in vivo.

Action of serine carboxypeptidase from paecilomyces carneus on oligopeptides containing carboxy-terminally amidated peptides

Paecilomyces carneus carboxypeptidase sequentially liberated amino acids from the carboxy-terminus of neurotensin, angiotensin I, bradykinin, and delta sleep-inducing peptide, indicating that the sequential hydrolysis of peptides was limited by the occurrence of intermediates with the structure of -Gly-X (X = L-amino acid), -Pro-X, -X-Gly, and -X-Pro. The enzyme had carboxyamidase and/or amidase activities for the carboxy-terminally amidated peptides. The enzyme essentially acted as a carboxyamidase for the long carboxy-terminally amidated peptides; an amidase became dominant for the substrates in the presence of bulky amino acids such as Arg, Met, Leu, and Phe in the penultimate (P1) and P2 positions, corresponding with the S1 and S2 sites of the enzyme, and the P3 position of carboxy-terminally amidated peptides played a significant role in the action as a carboxyamidase or a amidase.

Production, purification, and properties of serine carboxypeptidase from Paecilomyces carneus.

Seventeen strains of the genus Paecilomyces were examined for their ability to produce serine carboxypeptidase. Paecilomyces carneus IFO 7012 exhibited the highest potency for serine carboxypeptidase production. A maximum yield of serine carboxypeptidase was obtained by koji culture of the strain at 22 degrees C for 7 days. The serine carboxypeptidase was purified to homogeneity from an extract of the koji culture. The molecular weight of the enzyme was estimated to be 47,000 by HPLC. The isoelectric point of the enzyme was determined to be 4.0, and the optimum pH was 4.0 toward benzyloxycarbonyl-L-glutamyl-L-tyrosine (Z-Glu-Tyr) and benzyloxycarbonyl-L-phenylalanyl-L-alanine (Z-Phe-Ala), respectively. The enzyme was strongly inhibited by phenylmethylsulfonyl fluoride and p-chloromercurybenzoate. Relative hydrolysis rates of N-acylpeptides and kinetic studies indicated that the enzyme preferred substrates having bulky amino acids in the penultimate position from their carboxy-termini.

Promotion of plantlet formation from somatic embryos of carrot treated with a high molecular weight extract from a marine cyanobacterium.

Somatic embryos of Daucus carota L. developed into plantlets at high frequency after addition of an extract from a marine cyanobacterium, Synechococcus sp. NKBG 042902. High molecular weight, nondialyzing fraction, separated from the extract, possessed enhanced plantlet formation promoting activity. Plantlet formation frequency was 60 % after addition of nondialysate (100 mg/l) compared to 28 % without addition. Embryos treated with the nondialysate contained five times more chlorophyll than nontreated embryos after 6 days of culture. The chlorophyll a/b ratio of 4-day old treated somatic embryos was found to be similar to that of zygotic embryos. However, the chlorophyll a/b ratio of plantlets induced from nontreated somatic embryos was variable. Nondialysate was fractionated by ultracentrifugation and an active component obtained, which gave a maximum plantlet formation frequency of 71 %, and induced rapid greening of shoots.

Extracts of Marine cyanobacteria stimulated somatic embryogenesis of Daucus carota L.

Twenty five strains of marine cyanobacteria were screened for their ability to promote carrot somatic embryogenesis. Hot water extracts prepared from 21 of these strains promoted plantlet formation. Extracts from four strains increased plantlet numbers to an average of over 3.7-fold. Dialysates and nondialysates of each of these extracts also increased plantlet formation. For extracts from filamentous cyanobacteria, Nostoc sp. and Anabaena sp., dialysate was more effective (4.2-fold increase) than nondialysate (3.0-fold increase), whereas for unicellular strains Synechococcus sp. and Xenococcus sp., nondialysate was more effective (5.2-fold increase) than the dialysate (3.2-fold increase). These cyanobacterial extracts also promoted embryolike structure formation from two-year old carrot cell cultures which were unable to produce plantlets using the usual methods. Here, we demonstrate the existence in marine cyanobacterial extracts of low and high molecular weight factors which strongly promote somatic embryogenesis in carrot cell cultures.