Biomedical subjects

H Sakagami

Publications and source records attributed to H Sakagami.

At least 217 records · Page 12Linked to original sources

PubMedDate not supplied

Interaction between chlorogenic acid and antioxidants.

The interaction between chlorogenic acid (CGA) and antioxidants was investigated by two different parameters: radical intensity and cytotoxicity induction. ESR spectroscopy shows that CGA produced radicals under alkaline condition. The CGA radical was scavenged by 100-300-fold lower concentrations of sodium ascorbate or N-acetyl-l-cysteine (NAC), whereas the ascorbate radical was not completely scavenged by CGA. The cytotoxic activity of CGA against human oral tumor cells (HSC-2, HSG) was completely eliminated by lower concentrations of sodium ascorbate or NAC, whereas that of sodium ascorbate or NAC was only slightly reduced by CGA. The present study demonstrated that CGA induces cytotoxicity by its radical-mediated oxidation mechanism and suggests the applicability of ESR spectroscopy for the screening of drug to drug interaction.

Acetylcysteine↗

PubMedDate not supplied

Immunohistochemical detection of cytokeratin 18 and its neo-epitope in human salivary glands and pleomorphic adenomas.

An immunohistochemical method using a monoclonal antibody M30 (MAb M30), which reacts with the product released by the cleavage of cytokeratin 18 (CK18) by activated caspase, was used to investigate the extent of apoptosis in human salivary glands and pleomorphic adenomas. The distribution of CK18 in the salivary glands and adenomas was also determined and compared with that of the product detected by MAb M30. CK18 was detected in the cytoplasm of serous acinar and ductal cells in normal human salivary glands. In pleomorphic adenomas, CK18 was observed mainly in the tumor cells of duct-like structures, but not in those of myxomatous or chondroid tissues. Positive MAb M30 reaction products were found in the cytoplasm of acinar cells in the restricted lobules of normal salivary glands and in the luminal contents of duct-like structures in pleomorphic adenomas. These results suggest that a mechanism which suppresses apoptosis may be linked to the growth of human pleomorphic adenomas.

Adenoma, Pleomorphic↗

PubMedDate not supplied

Cytotoxicity and radical intensity of eugenol, isoeugenol or related dimers.

To investigate the possible link between radicals and cytotoxicity of eugenol-related compounds, dimer compounds were synthesized from eugenol (4-allyl-2-methoxyphenol) or isoeugenol (4-propenyl-2-methoxyphenol): bis-eugenol (3,3'-dimethoxy-5,5'-di-2-propenyl-1,1'-biphenyl-2,2'-diol); dehydrodiisoeugenol (2-(3-methoxy-4-hydroxyphenyl)-3-methyl-5-(1-propenyl)-7-methoxy-2,3- dihydrobenzofuran) and alpha-di-isoeugenol (r-l-ethyl-5-hydroxy-t-3-(4-hydroxy-3-methoxyphenyl)-6-methoxy-c-2- methylindane). Both the cytotoxic activity and the DNA synthesis inhibitory activity of these compounds against a salivary gland tumor cell line (HSG) and normal human gingival fibroblast (HGF) were decreased in the order of: dehydrodiisoeugenol, alpha-di-isoeugenol > isoeugenol > eugenol > bis-eugenol. Electron spin resonance (ESR) spectroscopy showed that dehydrodiisoeugenol, alpha-di-isoeugenol and eugenol, but not isoeugenol and bis-eugenol, produced phenoxyl radicals under alkaline condition (pH > 9.5). However, benzyl radicals were produced during the dimerization of isoeugenol to dehydrodiisoeugenol. The radical intensity of alpha-di- and dehydrodiisoeugenol appeared at relatively later incubation time than eugenol, suggesting that their phenoxyl radical was more stable than that of eugenol. Such a phenoxyl radical is produced by scavenging free radicals, during the inhibition of lipid peroxidation. Higher cytotoxic activity of isoeugenol dimers was thought to be induced by interaction with cell membranes via the lipophilic radical. The present study supports the notion that relative cytotoxicity of chemicals can be evaluated by measuring the radical intensity using ESR.

Antineoplastic Agents↗

PubMedDate not supplied

Cytotoxic activity of low molecular weight polyphenols against human oral tumor cell lines.

A total of 150 chemically-defined natural and synthetic polyphenols (flavonoids, dibenzoylmethanes, dihydrostilbenes, dihydrophenanthrenes and 3-phenylchromen-4-ones), with molecular weights ranging from 224 to 824, were investigated for cytotoxic activity against normal, tumor and human immunodeficiency virus (HIV)-infected cells. They showed higher cytotoxic activity against human oral squamous cell carcinoma HSC-2 and salivary gland tumor HSG cell lines than against normal human gingival fibroblasts HGF. Many of the active compounds had a hydrophilic group (hydroxyl group) in the vicinity of a hydrophobic group (prenyl, phenyl, methylcyclohexene or methylbenzene moiety), similar to isoprenoid-substituted flavones. Substitution of hydrophobic group (prenyl or geranyl group) did not significantly change the cytotoxic activity of flavanones, isoflavans, chalcones or 5-hydroxy-3-phenoxychromen-4-ones. However, the prenylation(s) of an isoflavone and a 2-arylbenzofuran significantly enhanced the cytotoxic activity. Agarose gel electrophoresis showed that active components induced internucleosomal DNA fragmentation in human promyelocytic leukemic HL-60 cells, but not in HSC-2 cells. Most of the polyphenols failed to reduce the cytophathic effect of HIV infection in MT-4 cells.

Anti-HIV Agents↗

PubMedDate not supplied

Effects of anticancer drugs, metals and antioxidants on cytotoxic activity of benzothiepins/benzoxepins.

Among 11 benzothiepins/benzoxepins, 4-chloro-3,4-dihydro-2-(2-oxo-2-phenylethyl)-1-benzothiepin-5-(2H)-one [1] showed the highest cytotoxicity against human oral squamous cell carcinoma HSC-2 cells, followed by 2,3-dihydro-2-(2-oxopropyl)-2-phenyl-1-benzoxepin [2]. Popular antioxidants, such as N-acetyl-L-cysteine and sodium ascorbate significantly reduced the cytotoxic activity of [1] but not that of [2]. Compound [1] induced internucleosomal DNA fragmentation in human promyelocytic leukemic HL-60 cell line, but produced large DNA fragmentation in human oral tumor cell lines (HSC-2, HSG). Compounds [1] and doxorubicin additively reduced the viable cell number of HSC-2 cells. These data, taken together with their tumor specific action, demonstrate for the first time, the medicinal efficacy of benzothiepins/benzoxepins.

Antineoplastic Agents↗

PubMedDate not supplied

Radical modulating activity and cytotoxic activity of synthesized eugenol-related compounds.

The ability of nine synthetic eugenol-related compounds to scavenge O2- (generated by the hypoxanthine-xanthine oxidase reaction) was compared with their radical generation and cytotoxic activity. ESR spectroscopy showed that eugenol (4-allyl-2-methoxyphenol), 2-allyl-4-methoxyphenol, 2-allyl-4-t-butylphenol and 2,4-dimethoxyphenol efficiently scavenged O2- and produced radicals under alkaline conditions. 2-allyl-4-t-butylphenol showed the highest cytotoxic activity and DNA-synthesis inhibitory activity, possibly due to the hydrophobic radical reactivity. 2-allyl-4-methoxyphenol and 2,4-dimethoxyphenol showed higher antioxidant activity than 3-t-butyl-4-hydroxyanisol (BHA), but all these compounds showed comparable cytotoxic activity with each other. These findings suggest a possible link between the cytotoxic activity and radical generation/scavenging activity in eugenol-related compounds.

Antineoplastic Agents↗

PubMedDate not supplied

Effect of cobalt ion on radical intensity and cytotoxic activity of antioxidants.

The effect of CoCl2 on the cytotoxic activity of various antioxidants against human oral tumor cell lines (HSC-2, HSG) and normal human gingival fibroblasts (HGF) was investigated. Noncytotoxic concentrations of CoCl2 significantly reduced the cytotoxic activity of sodium ascorbate, gallic acid, epigallocatechin gallate (EGCG), curcumin and dopamine, but not that of sodium 5,6-benzylidene-L-ascorbate (SBA) and benzaldehyde. Among these compounds, benzaldehyde showed the most prominent tumor-specific cytotoxic action. ESR spectroscopy showed that these antioxidants produced radicals under alkaline condition and that their radical intensity was transiently enhanced and finally disappeared by addition of CoCl2. Antioxidants which are sensitive to CoCl2 generally had higher cytotoxic activity and oxidation potential (measured by NO monitor) and addition of CoCl2 significantly reduced their oxidation potential. The present study suggests that cobalt ion stimulates the oxidation of antioxidants to their inactive products.

Antioxidants↗

PubMedDate not supplied

Effect of antioxidants on radical intensity and cytotoxicity of hydroquinone.

Hydroquinone (HQ) dose-dependently reduced the viable cell number of oral tumor cell lines (HSC-2, HSG). HQ induced internucleosomal DNA fragmentation in human promyelocytic leukemic HL-60 cells, but not in HSC-2 nor HSG cells. Cytotoxic activity of HQ was slightly reduced by catalase, but was enhanced by superoxide dismutase, suggesting the possible involvement of hydrogen peroxide in HQ-induced cytotoxicity. This was supported by slight increase or decrease of cytotoxicity of HQ in the presence of Cu2+ and Fe3+, respectively. Lower concentrations of sodium ascorbate, ascorbic acid and ascorbic acid 6-palmitate reduced both the radical intensity and cytotoxic activity of HQ, more efficiently than ascorbic acid 2,6-dipalmitate, in contrast to the cytotoxic action of these ascorbates at higher (millimolar) concentrations. Popular antioxidants such as N-acetyl-L-cysteine and cysteine also reduced the radical intensity and cytotoxic activity of HQ. The present study suggests that cytotoxic activity of HQ is generated by radical-mediated oxidation mechanism.

Antioxidants↗

PubMedDate not supplied

Cytotoxic activity of steroidal saponins against human oral tumor cell lines.

Three steroidal saponins showed higher cytotoxicity against human oral squamous cell carcinoma cell lines (HSC-2), as compared with normal human gingival fibroblasts HGF. Tumor specificity of saponins exceeded that of tannins and flavonoids. Agarose gel electrophoresis showed that saponins failed to induce internucleosomal DNA fragmentation, but produced large DNA fragments in both HSC-2 cells and human promyelocytic leukemic HL-60 cells. In contrast to epigallocatechin gallate or gallic acid, cytotoxic activity of saponins was not significantly affected by metals (Co2+, Cu2+, Fe3+) nor by antioxidants (sodium ascorbate, N-acetyl-L-cysteine, catalase). Furthermore, saponins did not produce radicals (detected by ESR spectroscopy) nor oxidation potential (measured by NO monitor). These data suggest that an oxidation-mediated mechanism is not involved in the cytotoxicity induced by steroidal saponins.

Antineoplastic Agents↗

PubMedDate not supplied

Cytotoxic activity of polyprenylalcohols and vitamin K2 derivatives.

Cytotoxic activity of 9 polyprenylalcohols and 6 vitamin K2 derivatives (MK-1 to MK-6) with various lengths of prenyl units was investigated. Among these compounds, geranylgeraniol with 4 prenyl units, and MK-2 with 2 prenyl units, showed the highest cytotoxic activity against human oral tumor cell lines (HSC-2, HSG), without induction of internucleosomal DNA fragmentation. Higher molecular weight compounds showed selective cytotoxicity against tumor cell lines than normal human gingival fibroblasts HGF. ESR spectroscopy showed that all polyprenylalcohols did not produce radical, nor scavenged O2- generated by hypoxanthine and xanthine oxidase reaction, and only slightly enhanced the radical intensity of sodium ascorbate. Vitamin K2 derivatives scavenged O2- more efficiently, but did not produce radical (except MK-3) and only slightly modified the ascorbate radical intensity. Cytotoxic activity of these compounds might be affected by the molecular weight, hydrophobicity, van der Waals area and stabilization of hydration of the molecule.

Acyclic Monoterpenes↗

PubMedDate not supplied

Biological activity of feijoa peel extracts.

Fractionated extracts of Feijoa peels were studied for cytotoxic activity, anti-human immunodeficiency virus (HIV) activity and antibacterial activity. Two most cytotoxic fractions A3 of acetone extract and M2 of methanol extract had potent inhibitory activity against Gram-positive and Gram-negative bacteria as well as fungi tested. Fraction A4 of acetone extract showed multidrug resistance (MDR)-reversal activity comparable with that of verapamil (positive control). These results indicate the therapeutic value of Feijoa peel extracts as potential antimicrobial and MDR-modulating agents.

Anti-Bacterial Agents↗

PubMedDate not supplied

Diverse biological activities of healthy foods.

Diverse biological activities of 7 healthy foods [powdered pine needle, citrate-fermented sesame, powdered coffee, royal jelly, propolis, pollen and white sesame oil (extracted by super critical state (40 degrees C, 350 atmospheric pressure))] were investigated. The pine needle, sesame and powdered coffee was also extracted successively by ethanol and hot water, and lyophilized. The pine needle and coffee extracts, and propolis showed higher in vitro cytotoxic, bactericidal and oxidation activity, as compared with other 4 lipophilic healthy foods. However, propolis showed slightly lower, but significant cytotoxic and bactericidal activity with much reduced oxidation potential. ESR spectroscopy demonstrated that the cytotoxic activity of these extracts was closely related to their radical generation and O2- scavenging activities. Healthy food components may have both pro-oxidant and anti-oxidant properties. Pre-treatment of mice with pine needle, sesame or powdered coffee extract significantly reduced the lethality of bacterial infection, possibly due to their host-mediated action. These extracts failed to reduce the cytophatic effect of HIV-1 (human immunodeficiency virus) infection in MT-4 cells. No apparent acute toxicity was detected in mice by oral administration of 10 g/kg of these extracts. This data suggest the medicinal efficacy of healthy foods.

Animals↗

PubMedDate not supplied

In vitro biological activity of prenylflavanones.

The biological activity of ten prenylflavanones purified from Sophora tomentosa L., and Sophora moorcroftiana Benth. ex Baker (Leguminosae) was investigated. The flavanones with prenyl-, lavandulyl- or geranyl groups on A ring, and two bioactive flavonostilbenes on ring B and stilbene (resveratrol) showed tumor-specific cytotoxic activity, antimicrobial activity, and anti-HIV activity, radical generation, and O2- scavenging activity. There was a positive relationship between radical generation and O2- scavenging activity in these prenylflavanones. These data suggest the medicinal significance of prenylflavanones.

Anti-HIV Agents↗

PubMedDate not supplied

Tumor-specific action of sodium 5,6-benzylidene-L-ascorbate in N-nitrosodiethylamine-administered mouse model.

In order to elucidate the mechanisms of antitumor action of sodium 5,6-benzylidene-L-ascorbate (SBA), we established a mouse hepatocellular carcinoma model by oral administration of N-nitrosodiethylamine (NDA) and examined the ascorbate radical intensity and putrescine content in the liver. The oral intake of NDA induced precancerous lesion and a significant increase in putrescine content among three major polyamines. When the oral intake of NDA was stopped, morphological changes were reversed. ESR spectroscopy showed that the homogenate of precancerous tissues produced greater amounts of ascorbate radical than that of normal liver tissue. Intravenous administration of SBA 30 minutes before removal of the liver prolonged the higher level of ascorbate radical generation in the homogenate of precancerous tissue. The antitumor activity of SBA might be due to the long-term production of radicals in tumor tissues by its prooxidant action.

Animals↗

PubMedDate not supplied

Diverse biological activity of polycaphenol.

Millimolar concentrations of alkaline extract of Cacao husk (polycaphenol) were more cytotoxic to human oral tumor cells (human oral squamous cell carcinoma HSC-2, human salivary gland tumor HSG), than to human gingival fibroblast (HGF), suggesting its tumor-specific action. Polycaphenol enhanced the radical intensity and cytotoxic activity of vitamin K3 more effectively than that of sodium ascorbate (vitamin C). Polycaphenol effectively scavenged the superoxide anion, produced by the hypoxanthine-xanthine oxidase reaction, indicating bimodal (prooxidant and antioxidant) action of polycaphenol. Polycaphenol inhibited the cytopathic effect of HIV (human immunodeficiency virus) infection in MT-4 cells, to a comparable extent as that achieved by lignin. Pretreatment of mice with polycaphenol protected them from lethal infection of Eschericia coli. These data suggest the medicinal efficacy of polycaphenol.

Animals↗

PubMedDate not supplied

Cytotoxic activity of 5-benzoylimidazole and related compounds against human oral tumor cell lines.

A total of 24 benzoylimidazoles and structurally-related compounds were investigated for their cytotoxic activity against oral tumor cells and normal gingival fibroblast. Compound 23 (5-(2-hydroxylbenzoyl)-2-phenylimidazole) showed the highest cytotoxic activity against both human oral tumor cell lines (human squamous cell carcinoma HSC-2, human salivary gland tumor HSG) and normal human gingival fibroblast (HGF). Compounds 7 (2-(2-hydroxybenzoyl)benz imidazo[2,1-b]thiazole), 14 (1,3-diethyl-5-(2-hydroxybenzoyl)-4-imidazoline-2-thione) and 18 (5-(2-hydroxy-4-methoxybenzoyl)-3-methyl-2-methylimino-4-thiazoline) showed slightly lower cytotoxic activity, but higher tumor-specific cytotoxic action. The cytotoxic activity of compound 23 was significantly reduced by CuCl2, but not by CoCl2, FeCl3, or by antioxidants (N-acetyl-L-cysteine, sodium ascorbate, catalase). Compound 23 did not show any detectable oxidation potential (determined by NO monitor). Agarose gel electrophoresis demonstrated that compound 23 induced DNA fragmentation in human promyelocytic leukemia cells HL-60, but not in HSG cells. These data suggested that the response to compound 23 might be different from cell to cell.

Antineoplastic Agents↗

PubMedDate not supplied

Cytotoxic activity of saponins from Camassia leichtlinii against human oral tumor cell lines.

Five steroidal saponins from Camassia leichtlinii showed higher cytotoxicity against human oral squamous cell carcinoma cells HSC-2, as compared to normal human gingival fibroblasts HGF. The tumor specificity of saponins varied considerably from sample to sample, but was generally higher than that of tannins, flavonoids and prenylated compounds such as geranylgeraniol and vitamin K2 (MK-2). Agarose gel electrophoresis showed that the saponins failed to induce internucleosomal DNA fragmentation, but produced large DNA fragments in HSC-2 cells, whereas two saponin samples (compounds 1 and 5) induced internucleosomal DNA fragmentation in human promyelocytic leukemic HL-60 cells. In contrast to epigallocatechin gallate or gallic acid, the cytotoxic activity of saponins was not significantly affected by metals (Co2+, Cu2+, Fe3+) or by antioxidants (sodium ascorbate, N-acetyl-L-cysteine, catalase). Furthermore, the saponins did not produce radicals (detected by ESR spectroscopy) nor oxidation potential (measured by NO monitor). These data suggest that an oxidation-mediated mechanism is not involved in the cytotoxicity induced by the steroidal saponins.

Antineoplastic Agents, Phytogenic↗

PubMedDate not supplied

Combination effect of lignin F and natural products.

We investigated the effect of lignin F, isolated from the alkaline extract of the cone of Pinus parviflora Sieb. et Zucc, on the cytotoxic activity and radical intensity (measured by ESR spectroscopy) of various natural products. Lignin F slightly inhibited the proliferation of human oral tumor cell lines (human squamous cell carcinoma HSC-2, human salivary gland tumor HSG), but not that of human gingival fibroblast HGF, suggesting its tumor specific cytotoxic action. Lignin F enhanced the cytotoxic activity of vitamin K2, vitamin K3, sodium ascorbate (vitamin C), epigallocatechin gallate (EGCG) (a major component of green tea), gallic acid (structural unit of tannin), chlorogenic acid, and 6 tea extracts (Japanese green tea, Japanese barley tea, black tea, Chinese green tea, Chinese Jasmin tea, Chinese Oolong tea), to various extents. On the other hand, lignin inhibited the cytotoxic activity of curcumin and dopamine. ESR spectroscopy demonstrated that combination of lignin and vitamin K3, EGCG or gallic acid synergistically augmented the radical intensity. Lignin F enhanced the bactericidal activity of EGCG against E. coli. These data suggest the beneficial effect of the combination of lignin F and natural products.

Antineoplastic Agents, Phytogenic↗