Biomedical subjects

K Fukuchi

Publications and source records attributed to K Fukuchi.

172 records · Page 10Linked to original sources

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

Induction of tumor degeneration by sodium benzylideneascorbate.

Intravenous administration of sodium benzylideneascorbate (SBA) rapidly necrotized inoperable human lung cancer, and induced degeneration of 3'-methyl-4-dimethylaminoazobenzene-induced rat hepatocellular carcinoma (vacuolar, eosinophilic degeneration, nuclear debris) without affecting the serum glutamic oxaloacetic transaminase, gamma-glutamyl transpeptidase and total protein levels. Cultured normal human lung and skin fibroblasts, and human glioma and glioblastoma cell lines were relatively resistant to SBA, when compared to human myelogenous leukemic cell lines. SBA had no apparent host immunopotentiation activity such as stimulation of cytokine action or production; activation of monocyte or polymorphonuclear cells; or modulation of poly (ADP-ribose) glycohydrolase activity. The data suggest that the antitumor activity of SBA might be produced by direct action of authentic SBA or its metabolized form(s), rather than by immunopotentiation of the hosts.

Animals↗

PubMedDate not supplied

Increased expression of the proto-oncogene, c-myc, in human neuroblastoma cells by reversible inhibition of cell growth.

Expression of the proto-oncogenes N-myc and c-myc in the human neuroblastoma cell line, IMR32, was examined after reversible inhibition of DNA synthesis by treatment with deferoxamine. After 48 h treatment with 10(-5) M deferoxamine, the number of c-myc expressing cells doubled, while N-myc expressing cells did not change. The expression level of c-myc in each cell also increased. These results suggested that the synthesis of cellular factor(s) involved in the degradation of c-myc RNA or its product was suppressed by reversible inhibition of cell growth. The regulatory mechanisms of expression of N-myc and c-myc may be distinct.

Cell Cycle↗

PubMedDate not supplied

Inhibition of herpes simplex virus infection by pine cone antitumor substances.

Several antitumor substances extracted from cones of various pine trees inhibited the plaque formation of Herpes simplex virus types 1 and 2 (HSV-1, HSV-2) strains in African green monkey kidney cells and human adenocarcinoma cells. The 50% effective dose of the most active fraction, Fr. VI (0.3 micrograms/ml) was 0.001 times its 50% cytotoxic dose (greater than 300 micrograms/ml). The anti-HSV activity of various pine cone extracts increased with their acidity. Identification of the polyphenol groups as donors of the acidity was further supported by the observation that the anti-HSV activity of the natural polyphenolic products, such as tannin and lignin, significantly exceeded that of other natural or chemically modified antitumor polysaccharides. An experiment using radiolabeled virus particles indicated that the anti-HSV effect of both Fr. VI and lignin was attributable to interference with virus adsorption to these cells rather than to inhibition of virus penetration into the cells.

Animals↗

PubMedDate not supplied

The increase of CD5LOW+NK cells in patients with multiple myeloma and plasmacytoma.

CD5 antigen is present on all normal alpha beta T cells and some B cells. Human NK cells do not usually express CD5 antigen, but we found a novel subset of CD5LOW (low density of CD5) positive (CD5LOW+) natural killer cells (NK cells) in patients with multiple myeloma (MM) and plasmacytoma. To detect CD5LOW+NK cells, we examined the lymphocytes of 23 patients with MM and plasmacytoma by flow cytometry. Five out of 23 patients had CD5LOW+NK populations. These patients had many more NK cells than the other patients in the peripheral blood and bone marrow. The CD5LOW+NK cells had CD2, low density of CD8, CD16 and CD56, but no CD3, CD19, or CD20. Most of the CD5LOW+NK cells had HLA-DR, unlike the CD5-NK cells. Sorted CD5LOW+CD16+ populations were large granular lymphocytes (LGL). The CD5LOW+NK cells had some lytic activity on K562 cells in a 4-hour 51Cr release assay. Our results indicate that there is a novel subset of NK cells in some patients with MM and plasmacytoma and that CD5LOW+NK cells may be associated with NK cell activation.

Adult↗

PubMedDate not supplied

Suppression of HL-60 cell proliferation by deferoxamine: changes in c-myc expression.

Deferoxamine, an iron chelating agent, inhibits growth of HL-60 cells in a dose-dependent fashion. This inhibition of proliferation was completely blocked by simultaneous addition of equal molar FeCl3, and FeCl3 added after 24 hours of deferoxamine treatment was also effective. After 48 hrs, however, the delayed addition failed to reverse growth inhibition by deferoxamine. We showed that deferoxamine-treated HL-60 cells become arrested in S phase rather than at G1/0 phase. Changes in c-myc expression were examined in these deferoxamine-treated cells. A rapid decline of c-myc RNA expression was followed by increased expression (1.6-fold over untreated controls). Similar results were obtained when the expression of c-myc protein was evaluated. These changes in c-myc expression may be involved in the growth inhibition of HL-60 cells by deferoxamine. These results are contrasted with the effects of the differentiation inducer, 1 alpha,25(OH)2D3.

Cell Cycle↗

PubMedDate not supplied

Induction of DNA fragmentation by tannin- and lignin-related substances.

A variety of tannin and lignin-related compounds were compared for their ability to induce nucleosome-sized DNA fragmentation (a biochemical hallmark of apoptosis), using agarose gel electrophoresis and a fluorescence activated cell sorter. Monomeric, dimeric, trimeric and tetrameric hydrolysable tannins induced nucleosome-sized DNA fragmentation in HL-60 cells, more potently than condensed tannins. The highest activity was detected in gallic acid, a component unit of tannins. Natural lignified materials, except for caffeic acid and its dehydrogenation polymer, showed much weaker activity. Protein-bound polysaccharide (PSK) was inactive. Gallic acid induced DNA fragmentation in four human myelogenous leukaemic cell lines, but not in human T-cell leukaemia and erythroleukaemia cell lines. Ca2+ depletion from the culture medium slightly, but significantly, reduced the apoptosis-inducing activity of gallic acid, but did not significantly affect that of tannic acid or caffeic acid. After treatment with gallic acid, intracellular Ca2+ concentration was significantly elevated. The apoptosis-inducing activity of polyphenols may further emphasize their medicinal efficacy.

Apoptosis↗

PubMedDate not supplied

Induction of DNA fragmentation in human myelogenous leukaemic cell lines by phenothiazine-related compounds.

A series of phenothiazine, benzo[a]phenothiazine and benz[c]acridine derivatives were compared for their ability to induce nucleosome-sized DNA fragmentation (a biochemical hallmark of apoptosis), using agarose gel electrophoresis and a fluorescence activated cell sorter. Significant DNA fragmentation-inducing activity was detected in 12H-benzo[a]phenothiazine, 5-oxo-5H-benzo[a]phenothiazine and 9-methyl-12H-benzo[a]phenothiazine, which induced the monocytic differentiation of human myelogenous leukaemic cell lines. On the other hand, an other three benzo[a]phenothiazines, six 10-[n-(phthalimido)alkyl]-2-substituted-10H-phenothiazines, six 1-(2-chloroethyl)-3-(2-substituted-10H-phenothiazin-10-yl)alkyl-1- ureas, and twelve benz[c]acridines showed little or no DNA fragmentation-inducing activity. Active benzo[a]phenothiazines induced DNA fragmentation in four human myelogenous leukaemic cell lines (HL-60, ML-1, U-937, THP-1), but not in human T-cell leukaemic MOLT-4 and erythroleukaemic K-562 cell lines, which were also resistant to other apoptosis-inducing agents. Ca2+-depletion from the culture medium did not significantly affect their DNA fragmentation-inducing activity. The differentiation and apoptosis-inducing activity of benzo[a]phenothiazines have an important role for their medicinal efficacy.

Acridines↗

PubMedDate not supplied

Effect of methionine depletion on growth and apoptosis in various tumor cell lines.

Sodium ascorbate, sodium 5,6-benzylidene-L-ascorbate (SBA), gallic acid and caffeic acid induced apoptotic cell death in human myelogenous leukemic cell lines, and stimulated oxidation of methionine into methionine sulfoxide in the culture medium. When various tumor cell lines were cultured in methionine-free medium, their growth was nearly terminated at G1 phase of the cell cycle, producing much smaller number of apoptotic cells. Addition of methionine sulfoxide to the methionine-free medium did not stimulate the apoptosis induction. These data suggest that induction of apoptosis by ascorbates, gallate or by caffeate cannot be simply explained by methionine oxidation.

Antioxidants↗

PubMedDate not supplied

Induction of DNA fragmentation by nicotine in human myelogenous leukemic cell lines.

The effect of nicotine, a component of tobacco, on the cytokine production and cell growth of various cultured cells was investigated. Nicotine did not stimulate, but rather inhibited the tumor necrosis factor production by human peripheral blood mononuclear cells at higher doses. Cytotoxic concentrations of nicotine did not induce the monocytic and granulocytic differentiation of human myelogenous leukemic cell lines (HL-60, ML-1). Nicotine induced internucleosomal DNA cleavage in these leukemic cell lines but not in human peripheral blood lymphocytes and polymorphonuclear cells. The fragmentation-inducing activity of nicotine was not prevented by simultaneous addition of ascorbic acid. Flow cytometry showed a slight increase in the number of G2 + M phase cells, before the appearance of the apoptosis peak. Nicotine transiently increased the intracellular calcium concentration to higher levels in leukemic cells than in normal leukocytes. These data suggest that the induction of DNA fragmentation requires elevation of intracellular calcium concentration above a certain threshold level.

Ascorbic Acid↗