Biomedical subjects

M Inagaki

Publications and source records attributed to M Inagaki.

473 records · Page 27Linked to original sources

PubMedDate not supplied

Production of hydrogen peroxide in cancerous tissue by intravenous administration of sodium 5,6-benzylidene-L-ascorbate.

We investigated whether the antitumor action of sodium 5,6-benzylidene-L-ascorbate (SBA) is mediated via oxidation-involved mechanism, in three different systems: 3'-methyl-4-dimethylaminoazobenzene (DAB)-induced rat hepatocellular carcinoma (in vivo), its homogenate (semi in vivo), and cultured cells (in vitro). Oral intake of DAB irreversibly produced hepatocellular carcinoma in rats, with a maximum incidence of carcinogenesis after 4 months. Intravenous administration of SBA induced vacuolar, eosinophilic degeneration and nuclear debris, producing greater amounts of ESR signal of ascorbate radical and hydrogen peroxide (H2O2)-derived chemiluminescence (CL) (H2O2-CL) in the cancerous tissue than in the normal tissue. When SBA was directly added to the homogenates, higher amounts of ascorbate radical and H2O2-CL were generated in cancerous tissues. When SBA was added to the RPMI1640 medium supplemented with 10% fetal bovine serum, methionine was oxidized to methionine sulfoxide and H2O2 was produced in amounts that sufficiently induce apoptotic cell death in human promyelocytic leukemic HL-60 cells. Cytotoxic activity of SBA was significantly reduced by catalase. These data suggest that antitumor activity of SBA in vivo might at least in part be due to H2O2, produced from SBA.

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PubMedDate not supplied

Dioxopiperazine derivative potentiates antitumor effect of methylglyoxal bis(cyclopentylamidinohydrazone) on human and mouse leukemia cells.

Antiproliferative effects of 1,1'-ethylenedi-4-isobutoxy-carbonyloxymethyl-3,5-d iox opiperazine (MST-16), an inhibitor of topoisomerase II, in combination with methylglyoxal bis (cyclopentylamidinohydrazone) (MGBCP), an inhibitor for polyamine biosynthetic enzymes, were investigated using cultured human lymphoid cells and leukemic mice. The combined treatment of human Molt 4B lymphoid cells with MST-16 and MGBCP resulted in greater suppressions of cellular polyamine and protein biosyntheses and decrease of cell number than in the cells treated with either drug alone. Inhibition of macromolecule biosyntheses by MGBCP was additively potentiated by simultaneous treatment with MST-16. In vivo experiments, the combination of MST-16 and MGBCP markedly prolonged the survival time of mice bearing P388 or L1210 leukemia. These results suggest that good antitumor activity of combined treatment with MST-16 and MGBCP resulted from the diminution of DNA condensation and cellular proliferation caused by inhibition of topoisomerase II with MST-16 and by polyamine depletion with MGBCP.

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PubMedDate not supplied

Effect of physiological fluids on radical intensity of sodium ascorbate and sodium 5,6-benzylidene-L-ascorbate.

The effect of various physiological fluids on the radical intensity of sodium ascorbate and sodium 5,6-benzylidene-L-ascorbate (SBA) was investigated using ESR spectroscopy. Blood from various animals did not significantly affect the radical intensity of both ascorbates, whereas the corresponding plasma fractions significantly enhanced the radical intensity. This suggests that some populations of blood cells might modify the interaction between plasma components and ascorbates. Saliva contained labile substance(s) which effectively reduced the ascorbate radical intensity. HPLC demonstrated the presence of endogenous ascorbate in rat liver and brain homogenates. When sodium ascorbate or SBA was incubated with any of these homogenates, their radical intensity was synergistically enhanced, but abruptly declined without any apparent ascorbate degradation. Incubation with homogenates elevated the radical intensity of SBA up to the level significantly higher than that of sodium ascorbate. The present data suggest that antitumor action of SBA might be mediated via the accelerated production of ascorbate radical in the target organ.

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PubMedDate not supplied

Relationship between radical intensity and cytotoxic activity of dopamine-related compounds.

Millimolar concentrations of dopamine (DA), norepinephrine (NE), and 3,4-dihydroxyphenylacetic acid (DOPAC) were cytotoxic to human promyelocytic leukemiC HL-60 cells. However, their metabolites (3,4-dihydroxymandelic acid (DOMA), 3-methoxytyramine (MT), normetanephrine (NMN)) and six synthetic derivatives (which have two OCH3 groups replacing two OH groups on catechol backbone) displayed much lower cytotoxic activity. Three active compounds, but not other less potent compounds, produced radicals under alkaline conditions. All active compounds significantly enhanced the decay of ascorbic acid endogenously present in rat brain homogenate, whereas all synthetic derivatives were inactive. Ascorbic acid induced apoptotic cell death in HL-60 cells and the apoptosis induction was significantly reduced by simultaneous addition of (DA). The cytotoxic activity of (DA) was also neutralized by ascorbic acid. These data suggest the possible interaction between (DA) and ascorbic acid.

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PubMedDate not supplied

Role of hydrogen peroxide in antitumor activity induction by sodium 5,6-benzylidene-L-ascorbate.

Role of hydrogen peroxide (H2O2) in the induction of antitumor activity against chemically-induced rat hepatocellular carcinoma by sodium 5,6-benzylidene-L-ascorbate (SBA) was investigated. ESR spectroscopy demonstrated that rat liver homogenate of cancerous tissue significantly enhanced the radical intensity of SBA more potently than that of precancerous or normal tissue. The peroxyoxalate chemiluminescence method demonstrated that SBA significantly enhanced the production of H2O2-derived chemiluminescence intensity in the liver homogenates, and the effect of SBA was greater in cancerous tissue than in precancerous or normal tissue. Addition of ascorbic acid, a degradation product of SBA, showed similar but slightly weaker stimulation effects. These data suggest that antitumor activity of SBA in vivo might, at least in part, be due to H2O2 production.

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