Biomedical subjects

Harukuni Tokuda

Publications and source records attributed to Harukuni Tokuda.

At least 55 records · Page 3Linked to original sources

PubMed2004

Cancer chemopreventive activity of serratane-type triterpenoids from Picea jezoensis.

To search for cancer chemopreventive agents from natural sources, 13alpha,14alpha-epoxy-21alpha-methoxyserratan-3-one, 21alpha-methoxyserrat-13-en-3-one, and 21alpha-hydroxy-3beta-methoxyserrat-14-en-30-al isolated from the cuticle of Picea jezoensis (Sieb. et Zucc.) Carr. var. jezoensis (Pinaceae) were investigated for inhibitory effects in a two-stage mouse skin carcinogenesis test on mouse skin with 7,12-dimethylbenz[a]anthracene (DMBA) as initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as promoter. 21Alpha-hydroxy-3beta-methoxyserrat-14-en-30-al and 13alpha,14alpha-epoxy-21alpha-methoxyserratan-3-one were found to exhibit strong antitumor-promoting activities in the in vivo carcinogenesis test.

Alkaloids↗

PubMed2004

Cancer chemopreventive effect of phenothiazines and related tri-heterocyclic analogues in the 12-O-tetradecanoylphorbol-13-acetate promoted Epstein-Barr virus early antigen activation and the mouse skin two-stage carcinogenesis models.

In continuation of our search for novel agents, we have investigated 29 phenothiazines and related tri-heterocyclic compounds as potential cancer chemopreventive agents in a short-term in vitro assay of Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Among the evaluated compounds, chlorpromazine, phenoxazine, ethylpropazine, 9-oxo-9H-thioxanthene-3-carbonitrile-10,10-dioxide, thiothixene and phenothiazine showed profound inhibition of EBV-EA in the in vitro assay. This activity was influenced by a modification of the phenothiazine ring. Replacement of nitrogen in the phenothiazine ring with sulfur atoms decreased the anti-tumor activity. Overall analysis showed that the simple tri-cyclic compound phenoxazine was the most active anti-tumor promoting compound in the test system. Therefore, we assessed the anti-tumor promoting effect of phenoxazine in vivo in two different chemical carcinogen-induced-promotion experimental models in mice namely the 7,12-dimethylbenz(a)anthracene (DMBA) initiated and TPA-promoted ICR mouse skin two-stage carcinogenesis protocol and the peroxynitrite (PN)-induced and TPA-promoted skin carcinogenesis in HOS:HR-1 mouse. Following tumor initiation with DMBA, topical application of 0.0025% phenoxazine to the dorsal initiated mouse skin resulted in a highly significant inhibition of TPA tumor promotion. The compound exhibited remarkable inhibitory effects on the mouse skin tumor promotion in terms of a reduction in tumor multiplicity (>50%) and incidence, accompanied by an extension of the tumor latency. In the PN-induced and TPA-promoted two-stage mouse skin carcinogenesis, oral administration of phenoxazine (0.0025%) for 2 weeks showed profound decrease in both the tumor incidence and burden by more than 20 and 80%, respectively, at 10 weeks of treatment. This was also accompanied by a 20% delay in the tumor latency period. In all the treatment groups, there was no toxicity due to phenoxazine in the treatment groups as compared to the control animals. These significant anti-tumor potentials of phenoxazine either via topical or oral administration might be due to the inherent cytotoxicity of these classes of compounds, which can be utilized in the prevention of development of overt tumors, immunopotentiation, induction of differentiation and apoptosis. In addition, since phenoxazine derivatives and other related phenothiazine compounds in use, as anti-psychotic agents without any reported adverse effect are known to pass the blood-brain barrier, they represent a new class of cancer chemopreventive agents with greater implication in the prevention of brain cancers.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2004

Dimeric flavonol glycoside and galloylated C-glucosylchromones from Kunzea ambigua.

A novel dimeric flavonol glycoside linked through a methylene group, kunzeagin A (1), and six new chromone C-glucosides, kunzeachromones A-F (2-7), were isolated along with seven known compounds from the leaf extract of Kunzea ambigua. The structures of these compounds were elucidated on the basis of spectroscopic analyses and chemical properties. Kunzeachromones A-F provided additional examples of galloylated C-glucosidic chromones occurring in the Myrtaceae. Kunzeagin A (1) and major constituents of this plant (6-C- and 8-C-glucosylchromones and their monogallates) exhibited potent inhibitory effects on activation of Epstein-Barr virus early antigen induced by 12-O-tetradecanoylphorbol 13-acetate in Raji cells.

Antigens, Viral↗

PubMed2004

Microbial transformation of isosteviol and inhibitory effects on Epstein-Barr virus activation of the transformation products.

Microbial transformation of isosteviol (2), a beyerane-type diterpenoid obtained from stevioside (1) by acid hydrolysis, yielded 7beta-hydroxyisosteviol (3), 11beta-hydroxyisosteviol (5), and 12beta-hydroxyisosteviol (6) by the fungus Aspergillus niger, 17-hydroxyisosteviol (7) by the fungus Glomerella cingulata, and 3 and 7-oxoisosteviol (4) by the fungus Mortierella elongate. The five metabolites, 3-7, along with 1 and 2 were 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 as a primary screening test for inhibitors of tumor promoters. All the diterpenes tested showed potent inhibitory effects, with the five metabolites 3-7 exhibiting more potent effects.

Antigens, Viral↗

PubMed2004

(+)- and (-)-syn-2-isobutyl-4-methylazetidine-2,4-dicarboxylic acids from the extract of Monascus pilosus-fermented rice (red-mold rice).

The structures of two enantiomeric azetidine-type amino acids isolated from the n-butanol-soluble fraction of the 70% ethanol extract of red-mold rice fermented with Monascus pilosus were established to be (+)- [1; (+)-monascumic acid] and (-)-syn-2-isobutyl-4-methylazetidine-2,4-dicarboxylic acids [2; (-)-monascumic acid] based on spectroscopic methods.

Dicarboxylic Acids↗

PubMed2004

Chemical constituents of Millettia taiwaniana: structure elucidation of five new isoflavonoids and their cancer chemopreventive activity.

We describe the isolation and identification of five new isoflavonoids, millewanins A (1), B (2), C (3), D (4), and E (5), together with six known isoflavonoids and three rotenoids, from the stems of Millettia taiwaniana collected in Japan. The major component, auriculasin (6), exhibited significant inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. The results of the present investigation indicate that 6 might be a valuable antitumor promoter.

Animals↗

PubMed2004

Chemical constituents of Glycosmis arborea: three new carbazole alkaloids and their biological activity.

As part of the phytochemical studies of the plant genus Glycosmis, the constituents of the plant Glycosmis arborea were investigated. Three new carbazole alkaloids named glybomines A (1), B (2), and C (3), along with known monomeric alkaloids belonging to the carbazole, quinazoline, furoquinoline, quinolone, and acridone classes, were isolated from stems of the plant collected at Mymensing in Dhaka, Bangladesh. Glybomine A (1) is the first example of a 2,5-oxygenated carbazole alkaloid from natural sources. As a primary screening test for anti-tumor promoters, nine alkaloids isolated from this plant have been tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) induction by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). All alkaloids tested showed inhibitory activity.

Alkaloids↗

PubMed2004

Cancer chemopreventive activity of rotenoids from Derris trifoliata.

A study of the chemical constituents of the stems of Derris trifoliata Lour. (Leguminosae) led to the isolation and identification of one new rotenoid, 6aalpha,12aalpha-12a-hydroxyelliptone ( 3), together with five other known rotenoids. In a search for novel cancer chemopreventive agents (anti-tumor promoters), we carried out a primary screening of five of the rotenoids isolated from the plant for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12- O-tetradecanoylphorbol 13-acetate (TPA) in Raji cells. The inhibitory activity of 3 was found to be equivalent to that of beta-carotene without any cytotoxicity. Deguelin ( 4) and alpha-toxicarol ( 5) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. This investigation indicated that rotenoids might be valuable anti-tumor promoters.

Animals↗

PubMed2004

A new seco-abietane-type diterpene from the stem bark of Picea glehni.

A new seco-abietane-type diterpenoid, 13S-hydroxy-9-oxo-9,10-seco-abiet-8(14)-en-18,10alpha-olide (1) along with a known lignan compound, pinoresinol (2) was isolated from the stem bark of Picea glehni (Fr. Schm.) Masters. Spectroscopic methods and chemical conversions were used to establish the structure of 1. In order to assess their cancer chemopreventive potential, the inhibition of Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) was examined for compound 1, its synthetic analogue, 9,10-seco-8S,13S-epoxy-abiet-8(14)-en-18,10alpha-olide (la) and 2. The inhibitory effect of la on EBV-EA induction was strong (0, 20.7, 67.1 and 89.2 % inhibition at 1000, 500,100 and 10 mol ratio/TPA). The IC50 of la was 226 mol ratio/32 pmol/TPA.

Abietanes↗

PubMed2004

Potential anti-tumor promoting activity of lupane-type triterpenoids from the stem bark of Glochidion zeylanicum and Phyllanthus flexuosus.

Four known lupane-type triterpenoids, glochidonol (1), glochidiol (2), lup-20(29)-ene-1beta,3beta-diol (3) and glochidone (3) were isolated from the stem bark of Glochidion zeylanicum. Previously, lupeol (5), lup-20(29)-ene-3beta,24-diol (6) and betulin (7) were isolated from the stem bark of Phyllanthus flexuosus. This study reports the assays of these lupane-type triterpenoids: all isolates 1-7 and synthetic analogues, glochidonyl acetate (1a), lup-20(29)-ene-1,3-dione (1b) and lup-20(29)-ene 3beta,24-diacetate (6a) were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA). Among them, the effects of compounds 2 (IC50 = 290 mol ratio/32 pmol TPA) and 3 (IC50 = 300) were stronger than the others. In addition, compound 2 exhibited a strong inhibitory effect on mouse skin tumor promotion in an in vivo mouse two-stage carcinogenesis test.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2004

3-epicabraleahydroxylactone and other triterpenoids from camellia oil and their inhibitory effects on Epstein-Barr virus activation.

The structure of a triterpenoid isolated from the nonsaponifiable lipid (NSL) of the seed oil of the camellia (Camellia japonica L.; Theaceae) was established to be (20S)-3beta-hydroxy-25,26,27-trisnordammaran-24,20-olide (1; 3-epicabraleahydroxylactone) on the basis of spectroscopic and chemical methods. Six other triterpenoids isolated from the NSL were identified as 3-epicabraleadiol (2), ocotillol II (3), ocotillol I (4), dammarenediol II (5), (20R)-taraxastane-3beta,20-diol (6), and lupane-3beta,20-diol (7). Upon evaluation of the seven triterpenoids (1-7) with respect to their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, three compounds (5-7) showed potent inhibitory effects against EBV-EA induction (IC(50) values of 277-420 mol ratio/32 pmol TPA).

Antigens, Viral↗

PubMed2004

Triterpene acids from the leaves of Perilla frutescens and their anti-inflammatory and antitumor-promoting effects.

Nine triterpene acids, viz., six of the ursane type, ursolic acid (1), corosolic acid (2), 3-epicorosolic acid (3), pomolic acid (4), tormentic acid (5) and hyptadienic acid (6), and three of the oleanane type, oleanolic acid (7), augustic acid (8) and 3-epimaslinic acid (9), among which 1 constituted the most predominant triterpene acid, were isolated and identified from ethanol extracts of the leaves of red perilla [Perilla frutescens (L.) Britton var. acuta Kudo] and green perilla [P. frutescens (L.) Britton var. acuta Kudo forma viridis Makino]. These eight compounds, 1, 2, 4-9, 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 0.09-0.3 mg per ear. In addition, an evaluation against the Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA showed five compounds, 1-3, 5 and 9, with a potent inhibitory effect on EBV-EA induction (91-93% inhibition at 1x10(3) mol ratio/TPA). Furthermore, compound 5 exhibited strong 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.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2003

Chalcones, coumarins, and flavanones from the exudate of Angelica keiskei and their chemopreventive effects.

From an ethyl acetate-soluble fraction of the exudate obtained from the stems of Angelica keiskei (Umbelliferae), 17 compounds, viz. five chalcones (1-5), seven coumarins (6-12), three flavanones (13-15), one diacetylene (16), and one 5-alkylresorcinol (17), were isolated. These compounds were evaluated with respect to their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, which is known to be a primary screening test for antitumor-promoters. With the exception of three compounds (10, 16, and 17), all other compounds tested showed potent inhibitory effects on EBV-EA induction (92-100% inhibition at 1x10(3)mol ratio/TPA). In addition, upon evaluation of these compounds for the inhibitory effects against activation of (+/-)-(E)-methyl-2-[(E)-hydroxy-imino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitric oxide (NO) donor, as a primary screening test for antitumor-initiators, two chalcones (2 and 3) and six coumarins (6-11) exhibited potent inhibitory effects.

Angelica↗

PubMed2003

Tumor chemopreventive activity of 3-O-acylated (--)-epigallocatechins.

In order to seek promising cancer chemopreventive agents, we assessed the antitumor promoting activities of 3-O-octanoyl- or 3-O-(2-methyloctanoyl)-(--)-epigallocatechins, inhibiting markedly the activation of Epstein-Barr virus early antigen, in a two-stage mouse skin carcinogenesis assay. As a result, these derivatives inhibited a papilloma formation 1.3-1.6-fold more strongly than (--)-epigallocatechin gallate well established as anti-tumor promoter.

Acylation↗

PubMed2003

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

As a continuation of our studies using natural and synthetic products as cancer chemopreventive agents, we examined the standard redox potentials of some naphthoquinones 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 naphthoquinones on Epstein-Barr virus early antigen activation. It has been further shown that the correlation can be enhanced by introducing an electronic property, i.e. the atomic charges at the C(4) and O(10) atoms in the quinone skeleton ring as additional parameters.

Animals↗

PubMed2003

Sterol ferulates, sterols, and 5-alk(en)ylresorcinols from wheat, rye, and corn bran oils and their inhibitory effects on Epstein-Barr virus activation.

Sterol ferulate, free sterol, and 5-alk(en)ylresorcinol constituents of wheat, rye, and corn bran oils were studied. Among the sterol ferulates, one novel compound, 24-methylenecholestanol ferulate (7), along with six known compounds, namely, 24-methylcholestanol ferulate (1), 24-methylcholesterol ferulate (2), 2-methyllathosterol ferulate (3), stigmastanol ferulate (4), sitosterol ferulate (5), and schottenol ferulate (6), were isolated and characterized. Five known free sterols, namely, 24-methylcholesterol (8), stigmastanol (9), sitosterol (10), schottenol (11), and stigmasterol (12), were isolated and identified. 5-Alk(en)ylresorcinols were found in wheat and rye bran oils but not in corn bran oil. Of these, one new compound, 5-n-(2'-oxo-14'-Z-heneicosenyl) resorcinol (19), and seven known compounds, namely, 5-n-heptadecyl- (13), 5-n-nonadecyl- (14), 5-n-heneicosyl- (15), 5-n-tricosyl- (16), 5-n-pentacosyl- (17), 5-n-(14'-Z-nonadecenyl)- (18), and 5-n-(2'-oxoheneicosyl)resorcinols (20), were isolated and characterized. These compounds were evaluated with respect to their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, which is known to be a primary screening test for antitumor promoters. Four compounds, 1, 2, 4, and 11, showed potent inhibitory effects on EBV-EA induction.

Coumaric Acids↗

PubMed2003

Anticarcinogenic activity of natural sweeteners, cucurbitane glycosides, from Momordica grosvenori.

To search for cancer chemopreventive agents from natural resources, many phytochemicals and food additives have been screened. Consequently, two natural sweeteners, mogroside V and 11-oxo-mogroside V isolated from the fruits of Momordica grosvenori, exhibited strong inhibitory effect on the primary screening test indicated by the induction of Epstein-Barr virus early antigen (EBV-EA) by a tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). These sweet glycosides, having cucurbitane triterpenoid aglycon, exhibited the significant inhibitory effects on the two-stage carcinogenesis test of mouse skin tumors induced by peroxynitrite (ONOO-) as an initiator and TPA as a promoter. Further, 11-oxo-mogroside V also exhibited the remarkable inhibitory effect on two-stage carcinogenesis test of mouse skin tumor induced by 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2003

Cancer chemopreventive activity of serratane-type triterpenoids on two-stage mouse skin carcinogenesis.

Eleven serratane-type triterpenoids isolated from the stem bark of Picea jezoensis (Sieb. et Zucc.) Carr. var. jezoensis (Pinaceae) and the stem bark of Picea jezoensis (Sieb. et Zucc.) Carr. var. hondoensis (Mayer) Rehder (Pinaceae) and three synthetic analogs were studied for their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). 21-Episerratenediol, serratenediol, diepiserratenediol, 3 beta-hydroxyserrat-14-en-21-one, 3 alpha-methoxy-21 beta-hydroxyserrat-14-en-16-one, 3 beta-methoxyserrat-14-en-21 beta-yl acetate, 3 alpha-methoxyserrat-14-en-21 beta-yl acetate and 3 beta-methoxyserrat-14-en-21 alpha-yl acetate demonstrated strong inhibitory effects on the EBV-EA activation without showing any cytotoxicity, their effects being stronger than that of a representative control, oleanolic acid. Furthermore, 21-episerratenediol exhibited a remarkable inhibitory effect on skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene as an initiator and TPA as a promoter. The result of the present investigation indicated that 21-episerratenediol might be valuable as a potent cancer chemopreventive agent.

Animals↗