Biomedical subjects

H Sakagami

Publications and source records attributed to H Sakagami.

At least 235 records · Page 13Linked to original sources

PubMedDate not supplied

Diverse biological activities of moxa extract and smoke.

Diverse biological activities of moxa extracts and smoke (gas phase) were investigated. Moxa was extracted with hot water (Fr. I), or ethanol (Fr. II), or extracted with hot water after ethanol wash (Fr. III) and then lyophilized to obtain the dried powders. Moxa smoke (containing a lot of gaseous components obtained by burning Moxa) (Fr. IV) was collected into phosphate-buffered saline and quantified spectrophotometrically. These extracts and Moxa smoke showed comparable cytotoxic activity against human oral tumor cell lines (HSC-2, HSG). Human gingival fibroblasts (HGF) were more resistant to any Moxa fractions. Neither of the extracts showed anti-HIV activity. Pretreatment of mice with Fr. I significantly reduced the lethal effect of E. coli infection. All extracts produced radicals under alkaline condition, with a maximum intensity at pH 10.5, and enhanced the radical intensity of sodium ascorbate. It was unexpected that these extracts show significant O2- scavenging activities. These data suggest the medicinal efficacy of Moxa extracts and smoke.

Animals↗

PubMedDate not supplied

Modification of apoptosis-inducing activity of gallic acid by saliva.

Gallic acid, a structural unit of tannin, induced apoptotic cell death, characterized by nuclear condensation and caspase activation in human oral tumor cell lines (HSC-2, HSG). Agarose gel electrophoresis demonstrated that gallic acid produced large DNA fragments in these cells, as well as in T-cell leukemia (MOLT-4) and erythroleukemia (K-562) cells, whereas it induced internucleosomal DNA fragmentation in human myelogenous leukemic cell lines (HL-60, ML-1, U-937, THP-1). This indicates that induction of internucleosomal DNA fragmentation or production of large DNA fragments depends on both target cells and inducers. Addition of total saliva dose-dependently reduced the cytotoxicity induction by gallic acid. These data suggested that the biological action of gallic acid might be modified by physiological fluids.

Antioxidants↗

PubMedDate not supplied

Biological activity of a fruit vegetable, "Anastasia green", a species of sweet pepper.

Russian green sweet pepper (Anastasia Green) was successively extracted with hexane, acetone, methanol and 70% methanol and the extracts were further separated into a total of twenty fractions by silica gel or ODS column chromatographies. The biological activities of these extracts and fractions were compared. The extracts and fractions showed higher cytotoxic activity against two human oral tumor cell lines than against normal human gingival fibroblasts, suggesting their tumor-specific action. Several fractions [H3, H4, A4] reversed the multidrug resistant gene (MDR1) against L5178 mouse T-cell lymphoma more effectively than (+/-) verapamil (positive control). All extracts and fractions showed no anti-human immunodeficiency virus (HIV) nor anti-Helicobacter pylori activity. These data suggest the medicinal importance of an Anastasia Green extract.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Cytotoxic activity of vitamins K1, K2 and K3 against human oral tumor cell lines.

Vitamin K1, K2 and K3 were compared for their cytotoxic activity, radical generation and O2- scavenging activity. Among these compounds, vitamin K3 showed the highest cytotoxic activity against human oral tumor cell lines (HSC-2, HSG), human promyelocytic leukemic cell line (HL-60) and human gingival fibroblast (HGF). Vitamin K3 induced internucleosomal DNA fragmentation in HL-60 cells, but not in HSC-2 or HSG cells. The cytotoxic activity of vitamins K2 and K1 was one and two orders lower, respectively, than K3. Vitamin K2, but not vitamin K3, showed tumor-specific cytotoxic action. ESR spectroscopy showed that only vitamin K3 produced radical(s) under alkaline condition and most potently enhanced the radical intensity of sodium ascorbate and scavenged O2- (generated by hypoxanthine-xanthine oxidase reaction system); vitamin K2 was much less active whereas vitamin K1 was inactive. These data suggest that the cytotoxic activity of vitamin K3 is generated by radical-mediated oxidation mechanism and that this vitamin has two opposing actions (that is, antioxidant and prooxidant), depending on the experimental conditions.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

Changes in amino acid pool and utilization during apoptosis in HL-60 cells induced by epigallocatechin gallate or gallic acid.

Recent studies have demonstrated the apoptosis-inducing potential of epigallocatechin gallate (EGCG), a major component of green tea, against various cultured cell lines. By using an amino acid analyzer, we investigated here the possible changes in the amino acid pool and utilization during the apoptosis of HL-60 cells induced by EGCG or gallic acid, a structural unit of tannin. Sublethal concentrations of EGCG initially elevated and then reduced the intracellular concentrations of most of amino acids except for glutamic acid and aspartic acid, whereas lethal concentrations of EGCG continuously reduced these amino acid pools during 6 hours. Both sublethal and lethal concentrations of gallic acid initially elevated and then reduced these amino acid pools. Both inducers elevated the intracellular accumulation and production of arginine and extensively reduced the utilization of other amino acids. These data demonstrate that EGCG showed more severe effects on the amino acid pool and utilization than gallic acid, which may explain, at least in part, the difference in apoptosis-inducing potential between these inducers.

Amino Acids↗

PubMedDate not supplied

Cytotoxic activity of benzothiepins against human oral tumor cell lines.

A total of 11 newly synthesized benzothiepins and structurally-related compounds were investigated for cytotoxic activity against both normal and tumor cells. All these compounds showed higher cytotoxic activity against three human oral tumor cell lines (HSC-2, HSC-3, HSG) than against normal human gingival fibroblast (HGF), suggesting tumor-specific cytotoxic action. In general, 3,4-dihydro-1-benzothiepin-5(2H)-ones [1-6] showed higher cytotoxic activity than 2,3-dihydro-1-benzothiepins [7-11]. Compounds 4 (4-bromo-3,4-dihydro-2-(2-oxo-2-phenylethyl)-1-benzothiepin-5(2H)-one), 5 (4-bromo-3,4-dihydro-2-(2-oxopropyl)-1-benzothiepin-5(2H)-one) and 6 (4-bromo-3,4-dihydro-2-[1-(methoxycarbonyl)-1-methylethyl]-1-benzothiepin-5(2H)-one), showed higher cytotoxic activity than compounds 1, 2 and 3, respectively, which had Cl instead of Br at C-4 position. Agarose gel electrophoresis demonstrated that these compounds induced large DNA fragments in oral tumor cells, whereas they produced smear pattern of smaller DNA fragments in human promyelocytic leukemia cells HL-60. These data suggest the medicinal efficacy of benzothiepins.

Antineoplastic Agents↗

PubMedDate not supplied

Production of hydrogen peroxide and methionine sulfoxide by epigallocatechin gallate and antioxidants.

Epigallocatechin gallate (EGCG) induced apoptosis-associated characteristics in human oral tumor cell lines more efficiently than ascorbates, gallic acid, vitamin K, flavonoids or steroidal saponins. Since catalase partially inhibited the cytotoxic activity of EGCG, the possible involvement of hydrogen peroxide (H2O2) in cell death induction was investigated, using TCPO chemiluminescence method. Production of H2O2 by EGCG, sodium ascorbate, gallic acid or catechin reached a maximum level within 30 minutes, and was increased up to a plateau level above pH 8. Under optimal conditions, 1 mM EGCG was converted to 1 mM H2O2. At neutral pH, EGCG produced the highest amount of H2O2, followed by gallic acid, sodium ascorbate and catechin. EGCG produced methionine sulfoxide from methionine in the culture medium, while the methionine oxidation by EGCG was significantly reduced in the presence of serum. ESR spectroscopy showed that EGCG, gallic acid and sodium ascorbate, but not catechin, produced radicals under alkaline condition and that all these compounds scavenged superoxide anion, produced by hypoxanthine-xanthine oxidase reaction. EGCG also effectively scavenged the ascorbate and gallate radicals, more efficiently than other compounds. These data suggest that the apoptosis induction by EGCG may be mediated by H2O2 produced in the culture medium.

Antineoplastic Agents↗

PubMedDate not supplied

Relationship between cytotoxic activity and radical intensity of isoflavones from Sophora species.

Among 11 isoflavones tested, genistein [YS13] produced higher cytotoxic activity against human oral tumor cell lines (HSC-2, HSG) than against normal cells (human gingival fibroblast, HGF), suggesting its tumor-specific action. Electron spin resonance (ESR) spectroscopy showed that YS13 did not produce radical, nor scavenged O2*- generated by hypoxanthine-xanthine oxidase reaction system, suggesting that radical-mediated oxidation mechanism is not be involved in the YS13-induced cytotoxicity. Addition of one prenyl group produced YS18 and YS19 with higher anti-Helicobacter pylori activity. Addition of two prenyl groups produced YS21 with the highest cytotoxic activity but lower tumor-specificity. Since YS21 produced the highest amount of radical and most efficiently scavenged O2*-, this compound may induce cytotoxicity by radical-mediated oxidation mechanism. All isoflavones failed to induce anti-human immunodeficiency virus (HIV) activity. These data suggest the medicinal efficacy of isoflavones.

Animals↗

PubMedDate not supplied

Cytotoxic and DNA damage-inducing activities of low molecular weight phenols from rhubarb.

Six new phenol (anthraquinone or stilbene) glycosides with an acyl group at 6-position of the glucopyranose moiety were isolated from rhubarb (the roots of Rheum palmatum) cultivated in Japan, together with 22 known compounds. Most of these compounds were evaluated for cytotoxic activity against tumor and normal cells and for induction of DNA damage by spore rec-assay. Among them, emodin and aloe-emodin showed higher cytotoxic activities against human oral squamous cell carcinoma (HSC-2) and salivary gland tumor (HSG) cell lines than against normal human gingival fibroblasts (HGF). Chrysophanol 8-O-beta-(6'-acetyl)glucopyranoside, 4-(4'-hydroxyphenyl)-2-butanone 4'-O-beta-D-(2"-O-galloyl-6"-O-cinnamoyl) glucopyranoside, and 6"-O-(4'''-hydroxybenzoyl) resveratroloside exhibited relatively higher cytotoxic activities against all these cells. The other glycosides of anthraquinone or stilbene showed weaker cytotoxic activity against these tumor cell lines, but may be considered as cancer chemopreventive agents. Spore rec-assay with a recombination deficient mutant of Bacillus subtilis M45 demonstrated the DNA damage-inducing activity of emodin and aloe-emodin 15-O-beta-D-glucopyranoside among, rhubarb phenols.

Bacillus subtilis↗

PubMedDate not supplied

Antioxidative activity of Allium victorialis L. extracts.

Allium victorialis L. (Liliaceae, "Hon-Gyoujya Nin-Niku" in Japanese) was successively extracted with hexane, acetone, methanol and 70% methanol and the extracts were further separated into a total of twenty-five fractions by silica gel and ODS column chromatographies. The biological activities of these four extracts and 25 column fractions were compared. The cytotoxic activity of all extracts and fractions against two oral tumor cell lines was significantly higher than that against normal human gingival fibroblasts, suggesting their tumor-specific action. Three methanol column fractions [M2, M3, M6] and a 70% methanol column fraction [70M6] most effectively reversed the multidrug resistance (MDR) against L5178 mouse T cell lymphoma. The electron spin resonance (ESR) spectroscopy showed that methanol column fractions and 70% methanol extracts produced the highest amount of radical(s) and most efficiently scavenging O2*-, generated by the hypoxanthine-xanthine reaction system, suggesting that the same substances in these fractions display both prooxidant and antioxidant properties. They showed no anti-human immunodeficiency virus (HIV) or anti-Helicobacterpylori activity. These data suggest the medicinal efficacy of Allium victorialis extract.

Allium↗

PubMedDate not supplied

Inhibition of chlorogenic acid-induced cytotoxicity by CoCl2.

Chlorogenic acid (CGA) induced apoptotic cell death in human oral squamous cell carcinoma (HSC-2) and salivary gland tumor (HSG) cell lines. CGA exhibited oxidation potential in the culture medium, as demonstrated by NO monitor. Both cytotoxic activity and oxidation potential were significantly reduced by the addition of CoCl2. ESR spectroscopy showed that CGA produced seven peaks of radicals under alkaline condition, while addition of CoCl2 altered the spectral pattern and diminished the radical intensity of CGA. CoCl2 accelerated the CGA-induced coloration of the culture medium and modified the difference spectrum at around 325 nm, an absorption maximum characteristic of CGA. These data suggest that CoCl2 induced conformational changes in the CGA molecule.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

Cytotoxic activity of 2-aminomethylene-3(2H)-benzofuranones against human oral tumor cell lines.

A total of 23 newly-synthesized 2-aminomethylene-3(2H)-benzofuranone and structurally-related compounds were compared for their cytotoxic activity against both normal (human gingival fibroblast HGF) and tumor cells (human oral squamous cell lines HSC-2, HSC-3 and human salivary gland tumor cells HSG). There was a significant variability of drug sensitivity among the oral tumor cell lines. In general, HSC-2 cells were the most sensitive, followed by HSG cells, while HSC-3 cells were the most resistant. HGF normal cells were highly resistant to all compounds, suggesting their tumor-specific cytotoxic action. The cytotoxic activity of the compounds with morpholine, 1-methylpiperazine or piperidine structure was generally elevated by the introduction of fluorine, but not chlorine and methoxy functional groups, to the benzofuranone structure, whereas that of compounds attached by 1-phenylpiperazine or 1-(2-pyridyl)piperazine was rather reduced. The most active compounds induced internucleosomal DNA fragmentation in human promyelocytic leukemia HL-60 cells, but not in HSG, further confirming that oral tumor cell lines are resistant to DNase digestion.

Antineoplastic Agents↗

PubMedDate not supplied

Synergistic cytotoxic action of vitamin C and vitamin K3.

We investigated the combination effect of sodium ascorbate (vitamin C) and menadione (vitamin K3) on the viability of various cultured cells. Human oral squamous cell carcinoma (HSC-2, HSC-3) and human promyelocytic leukemia (HL-60) cells were more sensitive to these vitamins as compared to normal cells (human gingival fibroblast HGF, human periodontal ligament fibroblast HPLF, human pulp cell HPC). The combination of vitamin C and vitamin K3 produced synergistic cytotoxicity against all these 6 cell lines. Treatment with vitamin C or vitamin K3, or their combination, induced internucleosomal DNA fragmentation only in HL-60 cells, but not in the oral tumor cell lines (HSC-2, HSC-3, HSG). ESR spectroscopy showed that vitamins C and K3 produce radicals under alkaline conditions and that the combination of these two vitamins synergistically enhanced their respective radical intensities.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Relationship between resonance energy and carcinogenic activity of benz[c]acridines.

In order to investigate the correlation between the carcinogenic activity of benz[c]acridines and the electron density, the Huckel orbital method was used. Resonance energies, circuit resonance energies and bond currents of benz[c]acridines were calculated by Aihara's TRE theory. It was shown that these compounds had very stable aromatic characters with positive resonance energies and that the resonance energies per pi-electron values for the compounds with lack of the double bond corresponding to the K-region from the parent skeleton were more stable than those of their parent compounds. 7-Methyl-benz[c]acridine derivatives with the methyl groups at 7-, 7, 9-, 7, 10-, 7, 11-, 7, 9, 10-, or 7, 9, 11-positions except 5, 7-dimethylbenz[c]acridine had potent carcinogenic activity and significantly lower resonance energy per pi-electron.

Acridines↗

PubMedDate not supplied

Induction of anti-Escherichia coli activity in mice by phenothiazines, benzo[a]phenothiazines and benz[c]acridines.

The abilities of 14 phenothiazines, 8 benzo[a]phenothiazines and 12 benz[c]acridines to induce anti-Escherichia coli activity in mice were compared. Pretreatment with several benzo[a]phenothiazines or benz[c]acridines protected mice from lethal infection of Escherichia coli in a dose-dependent manner, whereas most of the phenothiazines induced much weaker anti-Escherichia coli activity. However, direct contact of Escherichia coli with these compounds or their administration just after bacterial inoculation were ineffective. These data suggest the immunopotentiation activity of benzo[a]phenothiazines and benz[c]acridines.

Acridines↗

PubMedDate not supplied

Distribution of TNF endogenously induced by various immunopotentiators and Lactobacillus casei in mice.

Intravenous administration of heat-killed Lactobacillus casei YIT 9018 (LC) elicited endogenous cytotoxic factor (CF) production in ICR mice, peaking in serum after 2 h and declining gradually to basal level at 23 h. The endogenous CF production was significantly enhanced by priming with high molecular-weight lignins and glucans, but not by phenylpropenoid precursors or partially hydrolyzed products of glucans. The extent of stimulation of CF production by these priming agents was positively related to that of tumor necrosis factor (TNF) production, as judged by enzyme-linked immunosorbent assay. Endogenously produced TNF was concentrated more in liver, lung and intestine, as well as in serum, than in other organs. Histochemical examination revealed a significant increase in the number and swelling of Kupffer cells and sinusoidal endothelium in the liver of the treated mice.

Adjuvants, Immunologic↗

PubMedDate not supplied

O2- scavenging activity of lignins, tannins and PSK.

Iodination stimulators, such as the dehydrogenation polymer of caffeic acid (DHP-CA), a protein-bound polysaccharide (PSK), and a commercially available tannic acid, potently inhibited the luciferin-dependent chemiluminescence (LDCL) generated by opsonized zymosan-stimulated human peripheral blood polymorphonuclear cells (PMN). Continuous presence of these substances was necessary to express their inhibitory activity. The extent of inhibition paralleled their ability to scavenge the chemiluminescence generated by the xanthine-xanthine oxidase reaction. They also scavenged the chemiluminescence generated by potassium superoxide solution, but less effectively. An electron paramagnetic resonance spin-trapping technique revealed that DHP-CA significantly, but incompletely, scavenged O2-. The results suggest that O2- might be scavenged both directly by iodination stimulators, and by other oxygen radicals produced by activation of myeloperoxidase-mediated reaction.

Antibiotics, Antineoplastic↗

PubMedDate not supplied

Effect of lignins on HIV-induced cytopathogenicity and myeloperoxidase activity in human myelogenous leukemic cell lines.

We have previously reported the potent stimulation effect of lignin on the iodination of myeloperoxidase (MPO)-positive cells. We investigated here the anti-HIV (human immunodeficiency virus) activity of lignins in the MPO-positive (HL-60) and -negative (U-937) human myelogenous leukemic cell lines. Natural lignified material and dehydrogenation polymers, but not their precursors, effectively inhibited the cytopathic effect of HIV infection in both these cells as well as in MT-4 and MOLT-4 cells. HIV infection caused significant reduction of MPO activity in HL-60 cells, regardless of the presence or absence of lignins. These data suggest that MPO might not be involved in the anti-HIV activity induction by lignins.

Antiviral Agents↗