Biomedical subjects

Harukuni Tokuda

Publications and source records attributed to Harukuni Tokuda.

At least 37 records · Page 2Linked to original sources

PubMed2005

Cancer chemopreventive activity of lupane- and oleanane-type triterpenoids from the cones of Liquidamber styraciflua.

In a search for cancer chemopreventive agents from natural sources, four lupane-type and seven oleanane-type triterpenoids, and ten synthetic analogs were screened as potential anti-tumor promoters by using the in vitro short-term 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus early antigen (EBV-EA) activation assay. Among them, 25-acetoxy-3alpha-hydroxyolean-12-en-28-oic acid (1) and 3beta,25-epoxy-3alpha-hydroxylup-20(29)-en-28-oic acid (2) were examined for anti-tumor promoting activity in a two-stage carcinogenesis assay on mouse skin with 7,12-dimethylbenz[a]anthracene (DMBA) and TPA as promoter. 25-Acetoxy-3alpha-hydroxyolean-12-en-28-oic acid (1) and 3beta,25-epoxy-3alpha-hydroxylup-20(29)-en-28-oic acid (2) showed moderate inhibitory activities.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2005

Anti-tumor-initiating effects of monascin, an azaphilonoid pigment from the extract of Monascus pilosus fermented rice (red-mold rice).

Monascin (1) constitutes one of the azaphilonoid pigments in the extracts of Monascus pilosus-fermented rice (red-mold rice). Compound 1 was evaluated for its anti-tumor-initiating activity via oral administration on the two-stage carcinogenesis of mouse skin tumor induced by peroxynitrite (ONOO-; PN) or by ultraviolet light B (UVB) as an initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoter. Compound 1 exhibited marked inhibitory activity on both PN- and UVB-induced mouse skin carcinogenesis tests. These findings suggest that compound 1 may be valuable as potential cancer chemopreventive agent in chemical and environmental carcinogenesis.

Animals↗

PubMed2005

Anti-tumor-promoting activity of simple models of galactoglycerolipids with branched and unsaturated acyl chains.

Six new galactoglycerolipid analogs, in which one or two 4-methylpentanoyl or trans-2-butenoyl groups are linked to the 2-O-beta-D-galactosylglycerol skeleton, were tested for their anti-tumor-promoting activity using a short-term in vitro assay for Epstein-Barr virus early antigen (EBV-EA) activation. All these compounds were more active than their linear or saturated reference compounds in inhibiting the EBV activation promoted by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), the diester 1-O-(4-methylpentanoyl)-2-O-[6-O-(4-methylpentanoyl)-beta-D-galactopyranosyl]-sn-glycerol resulting the most active glycoglycerolipid analog till now tested. Four compounds (three butenoates and one 4-methylpentanoate), when tested in the in vivo two-stage carcinogenesis test, exhibited also inhibitory effects on mouse skin tumor promotion.

Animals↗

PubMed2005

Chemical constituents of Murraya siamensis: three coumarins and their anti-tumor promoting effect.

Isolation and structure elucidation of three coumarins, murrayacoumarins A, B, and C, together with eight known coumarins, from the leaves of Murraya siamensis Craib collected in Thailand are described. Results of a primary screening of inhibitory effects of seven of these compounds on 12-O-tetradecanoylphorbol-13-acetate-induced Epstein-Barr virus early antigen activation in Raji cells are also presented.

Antineoplastic Agents↗

PubMed2005

Cucurbitane-type triterpenoids from the fruit of Momordica charantia.

The structures of three new cucurbitane-type triterpenoids isolated from the methanol extract of the fruit of Japanese Momordica charantia were established as (19R,23E)-5beta,19-epoxy-19-methoxycucurbita-6,23,25-trien-3beta-ol (1), (23E)-3beta-hydroxy-7beta-methoxycucurbita-5,23,25-trien-19-al (2), and (23E)-3beta-hydroxy-7beta,25-dimethoxycucurbita-5,23-dien-19-al (3) on the basis of spectroscopic methods. These compounds were accompanied by the known (19R,23E)-5beta,19-epoxy-19,25-dimethoxycucurbita-6,23-dien-3beta-ol (4) and (19R,23E)-5beta,19-epoxy-19-methoxycucurbita-6,23-diene-3beta,25-diol (5). This is the first report of the isolation of tetracyclic triterpenoids possessing a delta23,25-conjugated diene system, viz., 1 and 2, from a natural source.

Fruit↗

PubMed2005

Oxygenated lanostane-type triterpenoids from the fungus ganodermalucidum.

Two new triterpenoids, 20(21)-dehydrolucidenic acid A (1) and methyl 20(21)-dehydrolucidenate A (2), and five new 20-hydroxylucidenic acids, 20-hydroxylucidenic acid D(2) (3), 20-hydroxylucidenic acid F (4), 20-hydroxylucidenic acid E(2) (5), 20-hydroxylucidenic acid N (6), and 20-hydroxylucidenic acid P (7), were isolated from the fruiting body of the fungus Ganoderma ludicum, and their structures were established on the basis of spectroscopic methods.

Lanosterol↗

PubMed2005

Antitumor-promoting activity of coumarins from citrus plants.

In order to identify antitumor-promoting agents, we performed primary in vitro screening of 31 coumarins isolated from 11 plants of the Citrus species (Rutaceae), examining their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12- O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Some of the 8-substituted coumarins, 8-formyl-7-hydroxycoumarin (5), osthenol (7), demethylauraptenol (8), osthenon (9) and dihydroosthenon (10), were found to significantly inhibit EBV-EA activation (IC50: 129-207 mol ratio/32 pmol TPA). Osthenol (7) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2005

Antitubercular activity and inhibitory effect on Epstein-Barr virus activation of sterols and polyisoprenepolyols from an edible mushroom, Hypsizigus marmoreus.

Seven sterols (1-7) and eight polyisoprenepolyols (8-15), isolated from the non-saponifiable lipid fraction of the dichloromethane extract of an edible mushroom, Hypsizigus marmoreus (Buna-shimeji), were tested for their antitubercular activity against Mycobacterium tuberculosis strain H37Rv using the Microplate Alamar Blue Assay (MABA). Six sterols (2-7) and two polyisoprenepolyols (8, 12) showed a minimum inhibitory concentration (MIC) in the range of 1-51 microg/ml, while the others (1, 9-11, 13-15) were inactive (MIC>128 microg/ml). The seven sterols (1-7) and three polyisoprenepolyols (8, 10, 12) were further evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Sterols 6 and 7 showed potent inhibitory effects while preserving the high viability of Raji cells.

Agaricales↗

PubMed2005

Anti-inflammatory and antitumor-promoting effects of the triterpene acids from the leaves of Eriobotrya japonica.

Sixteen triterpene acids, viz., five of the oleanane-type (1-5), nine of the ursane-type (6-14), and two of the lupane-type (15, 16), were isolated and identified from the ethyl acetate-soluble fraction of the methanol extract of the leaves of loquat, Eriobotrya japonica LINDL. (Rosaceae). Twelve of these compounds, 1-4, 6, 8-13, and 15, were evaluated for their inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg/ear) in mice. All the compounds tested showed a marked anti-inflammatory effect, with a 50% inhibitory dose (ID50) of 0.03-0.43 mg per ear. In addition, an evaluation against the Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA for all of the compounds, 12 and 13 showed potent inhibitory effects on EBV-EA induction. Furthermore, euscaphic acid (12) exhibited marked antitumor-promoting activity in an in vivo two-stage carcinogenesis test of mouse tumor by using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.

Animals↗

PubMed2004

Correlation between reduction potentials and inhibitory effects on Epstein-Barr virus activation of poly-substituted anthraquinones.

As a continuation of our studies using natural and synthetic products as cancer chemopreventive agents, we examined the reduction potentials of some poly-substituted anthraquinones in phosphate buffer at pH 7.2 by means of cyclic voltammetry. A definite correlation has been found between the reduction potentials and the inhibitory effects of the poly-substituted anthraquinones on Epstein-Barr virus early antigen activation. It has been further shown that the correlation can be enhanced by introducing log P as an additional parameter.

Anthraquinones↗

PubMed2004

Effect of exercise on hepatic gene expression in rats: a microarray analysis.

Exercise has various beneficial effects on liver function, enhancing both nutrient metabolism and antioxidant capacity. To explore the molecular mechanisms underlying these changes, we used a high-density cDNA microarray containing probe sets for 2,845 genes to analyze changes of gene transcription in the livers of rats after 4 weeks of running exercise. In comparison with sedentary animals, 105 genes were up-regulated and 86 genes were down-regulated, including genes with unknown functions. In addition, we detected an increase of p38 mitogen-activated protein kinase and protein and of the protein for signal transducer and activator of transcription 3 (stat3), corresponding to the increase of these mRNAs shown by microarray analysis. These results indicate that long-term exercise can alter liver function via changes of gene expression, especially the genes encoding signal transduction proteins such as p38 and stat3.

Animals↗

PubMed2004

Cancer chemopreventive activity of 3beta-methoxyserrat-14-en-21beta-ol and several serratane analogs on two-stage mouse skin carcinogenesis.

3beta-Methoxyserrat-14-en-21beta-ol (1) and 3alpha-methoxyserrat-14-en-21beta-ol (2) are the most abundant triterpenoids from two Picea plants, Picea jezoensis (Sieb. et Zucc.) Carr. var. jezoensis and P. jezoensis (Sieb. et Zucc.) Carr. hondoensis (Mayr) Rehder, and the total yield of 1 and 2 reach over 1/3 of the chloroform extract of the above two plants. This study deals with the potential of anti-tumor promoting activity of 1 and results of the assay of 22 synthetic serratane-type triterpenoids (6)-(27) derived from 1, 2, 21-episerratenediol (3), diepiserratenediol (4) and 13alpha,14alpha-epoxy-3beta-methoxyserratan-21beta-ol (5) to discuss the structure-activity relationship. As a preliminary evaluation of their potential to inhibit tumor promotion, the inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) were used. All compounds except for 12 and 19 showed potent inhibitory effects on EBV-EA induction (100% inhibition at 1000 mol ratio/TPA), their effects being stronger than that of a positive control oleanolic acid. Compounds 1, 13, 14, 18, 20 and 26 were selected to examine the effect on the in vivo two-stage mouse skin carcinogenesis test induced by 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. The most abundant triterpenoid 1 and the synthetic compounds 13 and 14 were found to exhibit the excellent anti-tumor promoting activity in the in vivo carcinogenesis test, and compounds 18, 20 and 26 also showed strong inhibitory effects.

Animals↗

PubMed2004

Cancer chemopreventive activity of phenylpropanoids and phytoquinoids from Illicium plants.

In our joint project involving search of anti-tumor promoters from natural plant sources, six phenylpropanoids and seven phytoquinoids isolated from three Illicium plants (Illiciaceae) were tested for their inhibitory activities against Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. All tested compounds showed inhibitory activity against the EBV-EA activation even at 1 x 10mol ratio, and the inhibitory activity of their compounds was found to be more than that of beta-carotene. Two phenylpropanoids having prenyl group, 4-allyl-2-methoxy-6-(3-methyl-2-butenyl)phenol (3) and 4-allyl-2,6-dimethoxy-3-(3-methyl-2-butenyl)phenol (4), showed more potent activities as anti-tumor promoters (IC50 224 and 217 mol ratio/TPA, respectively). The presence of a prenyl moiety in the phenylpropanoids plays an important role in anti-tumor promoting activity as xanthone, coumarin and flavonoid previously reported. This investigation indicated that prenylated phenylpropanoids might be valuable as potential cancer chemopreventive agents.

Antigens, Viral↗

PubMed2004

Multidrug-resistant cancer cell susceptibility to cytotoxic quassinoids, and cancer chemopreventive effects of quassinoids and canthin alkaloids.

Twenty-three quassinoids (1-23), which were isolated previously from Simaroubaceous plants, were evaluated for cytotoxicity against three multidrug-resistant cancer cell lines, KB-VIN, KB-7d, and KB-CPT. Nine compounds (2-7 and 9-11) showed significant cytotoxicity in all three cell lines. Compounds 1, 12-14, 17, and 20 demonstrated significant activity against the KB-7d and KB-CPT cell lines, and compounds 18, 19, and 23 revealed notable activity only against KB-7d cells. Structure-activity relationships were drawn based on these data. In addition, six quassinoid derivatives (24-29) and four canthin alkaloids (30-33), which were isolated from Brucea antidysenterica, were examined for their inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA) induced Epstein-Barr virus early antigen (EBV-EA) activation as cancer chemopreventive agents. All of these compounds demonstrated significant inhibitory effects against EBV-EA activation.

Alkaloids↗

PubMed2004

Correlation of redox potentials and inhibitory effects on Epstein-Barr virus activation of 2-azaanthraquinones.

As a continuation of our studies using natural and synthetic products as cancer chemopreventive agents, we examined the standard redox potentials of some 2-azaanthraquinones in phosphate buffer at pH 7.2 by means of cyclic voltammetry. A definite correlation has been found between the redox potentials and the inhibitory effects of the 2-azaanthraquinones on Epstein-Barr virus early antigen (EBV-EA) activation. It has been further shown that the correlation can be enhanced by introducing an electronic properties, i.e. the atomic charges at the C5 and O12 atoms in the quinone skeleton ring and the HOMO energy as additional parameters.

Anthraquinones↗

PubMed2004

Cancer chemopreventive effects of polyunsaturated fatty acids.

The inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), in Raji cells as a primary screening test for anti-tumor promoters, for 22 fatty acids (as free and esterified forms), including 10 di- and polyunsaturated acids, and the inhibitory effects on activation of (+/-)-(E)-methtyl-2-[(E)-hydroxy-imino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitric oxide (NO) donor, as a primary screening test for anti-tumor initiators, for 17 fatty acids (as methyl ester forms), were evaluated. Among the fatty acids tested, three n-3 polyunsaturated acids, eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), exhibited potent inhibitory effects both on EBV-EA and NOR 1 activation. Furthermore, DHA methyl ester exhibited remarkable anti-tumor-promoting activity on an in vivo two-stage carcinogenesis test of mouse tumor using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.

Animals↗

PubMed2004

Cancer prevention by antioxidants.

Various antioxidants in foods, such as phenolic compounds and carotenoids, were proven to have anticarcinogenic activity. In the case of carotenoids, the mixture of them was found to be very effective. In fact, the development of hepatoma in the high risk group of liver cancer, was significantly suppressed by the treatment with natural carotenoids mixture. The role of nitric oxide (NO) in carcinogenesis has been pointed out, since large quantity of NO has been detected in cancer tissues, and the expression of inducible NO synthase (iNOS) was found to correlate with tumor growth and metastasis. Recently, we found that NO possessed tumor initiating activity in mouse skin carcinogenesis. It has been suggested that some parts of pathological effects induced by NO may depend on peroxynitrite, an active metabolite of NO. Thus, we accessed the tumor initiating activity of peroxynitrite, and found that treatment with peroxynitrite (initiator) plus TPA (promoter) resulted in the formation of skin tumors. Under this experimental condition, it has been proven that natural antioxidants, such as curcumin and nobiletin, showed anti-tumor initiating effect. In the case of nobiletin, suppressive effect on iNOS induction has also been demonstrated. It is of interest that suppression of iNOS induction was also observed in phytoene synthase transgenic mouse. After administration of glycerol (a lung tumor promoter), lower induction of iNOS gene was observed in lung of the phytoene producing mice, comparing with that of control mice. Combinational use of various kinds of antioxidants distributed in foods, e.g., mixture of carotenoids and flavonoids, seems to be effective methods for cancer prevention.

Animals↗

PubMed2004

Citrus nobiletin inhibits azoxymethane-induced large bowel carcinogenesis in rats.

The inhibitory effects of dietary feeding of citrus nobiletin on azoxymethane (AOM)-induced rat colon carcinogenesis using a long-term bioassay were investigated. Five-week old male F344 rats were initiated with two weekly subcutaneous injections of AOM (20 mg/kg bw) to induce colonic tumors. They were also given the diets containing 0.01% or 0.05% nobiletin for 34 weeks, starting one week after the last dosing of AOM. At the end of the study, the incidence of colonic adenocarcinoma were 67% in the AOM alone group, 55% in the AOM-->0.01% nobiletin group, 35% (p<0.05) in the AOM-->0.05% nobiletin group. Also, nobiletin feeding reduced the cell-proliferation activity, increased the apoptotic index, and decreased the prostaglandin E2 content in colonic adenocarcinoma and/or colonic mucosa. These findings might suggest that citrus nobiletin has chemopreventive ability against AOM-induced rat colon carcinogenesis.

Animals↗