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Biomedical subjects

A Ozeki

Publications and source records attributed to A Ozeki.

7 recordsLinked to original sources

4-Aza-2,3-dehydro-4-deoxypodophyllotoxins: simple aza-podophyllotoxin analogues possessing potent cytotoxicity.

4-Aza-2,3-dehydro-4-deoxypodophyllotoxin analogues 3a-n were synthesized through quinolines 2a-n. Comparison of their cytotoxicity against P-388 leukemia cells revealed that the steric effects of the ring B substituents on the activity are greater than the electronic effects, while the presence of a methoxy group on the ring E is not essential to exhibit potent cytotoxicity. Analogues 3a and 3b proved to be more than twice as cytotoxic as natural podophyllotoxin (1).

Antineoplastic Agents, Phytogenic↗

Retinoic acid repressed the expression of c-fos and c-jun and induced apoptosis in regenerating rat liver after partial hepatectomy.

Retinoic acid (RA), which was injected within 4 h after partial hepatectomy (PH), inhibited DNA synthesis in regenerating liver. The inhibition was accompanied by apoptosis, evidenced by in situ end labeling and gel electrophoresis of DNA fragmentation. Characteristic DNA fragmentation was obvious at 4 h and reached a maximum at 8 h after injection. Northern blot analysis revealed that RA repressed the expression of c-fos and c-jun at 15 and 30 min with the up-regulation of retinoic acid receptor gamma (RARgamma) and RARbeta at 2 h after PH. The transglutaminase II mRNA level and activity were increased by RA injection at 4 h and 8 h after PH, respectively. The mRNA levels of thymidylate synthase and thymidine kinase, which are rate determining enzymes of DNA synthesis, decreased in RA injected rats. No change was seen in the expression of p53 and p21WAF1/CIP1 which have been suggested to participate in the apoptosis process. These results suggest that RA exerts the antiproliferative activity only on the early stage of liver regeneration accompanied by the repression of c-fos and c-jun expression and induction of apoptosis.

Animals↗

Cytotoxic quassinoids from Simaba cedron.

Four new quassinoids, cedronolactones A-D (1-4), together with nine known compounds, simalikalactone D (5), chaparrinone (6), chaparrin (7), glaucarubolone (8), glaucarubol (9), samaderine Z (10), guanepolide (11), ailanquassin A (12), and polyandrol (13), were isolated from the wood of Simaba cedron. The chemical structures of 1-4 were elucidated on the basis of their chemical and spectral properties. Cedronolactone A (1) was shown to exhibit a significant in vitro cytotoxicity (IC50 0.0074 microg/mL) against P-388 cells.

Alkaloids↗

Ethanol represses thymidylate synthase and thymidine kinase at mRNA level in regenerating rat liver after partial hepatectomy.

The effects of ethanol on liver regeneration after partial hepatectomy were investigated. The injection of ethanol inhibited the increases in the activities of thymidylate synthase and thymidine kinase in regenerating rat liver at 24 h after partial hepatectomy in a dose-dependent manner, with a concomitant reduction in DNA content. Northern blot analysis showed that the inhibition of thymidylate synthase and thymidine kinase activities was caused by comparable decreases in their mRNA levels. The immunoblotting assay confirmed the protein levels of thymidylate synthase and thymidine kinase as proportional to the activity and mRNA levels. These findings suggest that ethanol inhibits DNA synthesis by the repression of mRNA levels of dTMP-synthesizing enzymes during liver regeneration.

Animals↗