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TOSHIKAZU OKI, YOKO YAMAZAKI, NOBUHIRO NOMURA, TAMOTSU FURUMAI, YASUHI ...
1999 Volume 52 Issue 5 Pages
449-454
Published: May 25, 1999
Released on J-STAGE: September 19, 2008
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Cell surface oligosaccharides play a role in a variety of biological events such as cell adhesion and signal transduction. We have shown that BMY-28864, a semi-synthetic analog of pradimicin, induced apoptosis of U937 cells which had been incubated with 1-deoxymannojirimycin, an inhibitor of mannosidase I. BMY-28864 was not cytotoxic to the cells which had been cultivated with other glycosidase inhibitors such as castanospermine and swainsonine. We thus propose that BMY-28864 induces apoptosis by acting on a specific mannose-rich oligosaccharide, presumably (Man)
9(GlcNAc)
2.
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TOSHIKAZU OKI, YOKO YAMAZAKI, NOBUHIKO NOMURA, TAMOTSU FURUMAI, YASUHI ...
1999 Volume 52 Issue 5 Pages
455-459
Published: May 25, 1999
Released on J-STAGE: September 19, 2008
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Pradimicin (PRM) induces apoptosis in mammalian cells which had been incubated with 1-deoxymannojirimycin (DMJ). Flow cytometric analysis revealed that PRM preferentially induced apoptosis to the cells of the G1 phase. Two possible mediators in this apoptotic cascade were identified. Exposure of DMJ-treated cells to PRM resulted in a rapid (-5 seconds) and slow (-30 minutes) elevation of the intracellular calcium level. Reactive oxygen species (ROS) were proved to be involved in this system by the fact that the apoptosis was completely inhibited by treating the cells with a ROS scavenger,
N-acetylcysteine in prior to the PRM stimulation.
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III. Inhibitory Properties
KEITAROU SUZUKI, MASARU YAMAIZUMI, SATOSHI TATEISHI, YUTAKA MONNAI, MA ...
1999 Volume 52 Issue 5 Pages
460-465
Published: May 25, 1999
Released on J-STAGE: September 19, 2008
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A novel inhibitor of topoisomerases designated as topostatin was isolated from the culture filtrate of
Thermomonospora alba strain No. 1520. The inhibitory activity of topostatin was shown to be pH- and temperature-dependent with a maximum around at pH 6 and 28°C. The stability of topostatin decreased with decreasing pH and rising temperature. Topostatin inhibited topoisomerases I and II in a competitive manner with respect to DNA. The inhibitor also inhibited some restriction endonucleases such as
ScaI,
HindIII and
PstI, but not
AluI,
BamHI,
EcoRI, RNase A, DNase I, DNase II and DNA ligase. Topostatin did not induce the nuclear accumulation of p53 protein by DNA damage in the normal human cells.
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I. Taxonomy, Fermentation, Isolation and Biological Activity
JEAN-JACQUES SANGLIER, VALERIE QUESNIAUX, THEODOR FEHR, HANS HOFMANN, ...
1999 Volume 52 Issue 5 Pages
466-473
Published: May 25, 1999
Released on J-STAGE: September 19, 2008
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A novel class of macrolides for which the name sanglifehrins is proposed, has been discovered from actinomycete strains based on their high affinity binding for cyclophilin A (CypA), an immunophilin originally identified as a cytosolic protein binding cyclosporin A (CsA). The sanglifehrins were produced by
Streptomyces sp. A92-308110. They were isolated and purified by extraction and several chromatographic, activity-guided steps. Sanglifehrins A and B exhibit a 10-20 fold higher affinity for CypA than CsA, whereas the affinity of sanglifehrins C and D for CypA is comparable to that of CsA. Sanglifehrins exhibit a lower immunosuppressive activity than CsA when tested in the mixed lymphocyte reaction. Their
in vitro activity indicates that they belong to a novel class of immunosuppressants.
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II. Structure Elucidation, Stereochemistry and Physico-chemical Properties
THEODOR FEHR, JÖRG KALLEN, LUKAS OBERER, JEAN-JACQUES SANGLIER, W ...
1999 Volume 52 Issue 5 Pages
474-479
Published: May 25, 1999
Released on J-STAGE: September 19, 2008
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A novel class of macrolides, the sanglifehrins, was discovered by screening of actinomycete strains with a cyclophilin-binding assay. The chemical structures and absolute stereochemistries of the sanglifehrins A, B, C and D were determined unambiguously by NMR-techniques and by X-ray crystallography of the complex with cyclophilin A. Sanglifehrin A consists of a 22-membered macrocycle containing a tripeptide subunit and features in position 23 a chain of nine carbon atoms bearing a spirocyclic substituent. Sanglifehrins A and B are genuine metabolites whereas sanglifehrins C and D are artefacts.
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IV. Comparative Studies of UK-2A with Antimycin A3 on Cytotoxic Activity and Reactive Oxygen Species Generation in LLC-PK1 Cells
HIROAKI TAKIMOTO, KIYOTAKA MACHIDA, MASASHI UEKI, TOSHIO TANAKA, MAKOT ...
1999 Volume 52 Issue 5 Pages
480-484
Published: May 25, 1999
Released on J-STAGE: September 19, 2008
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UK-2A, a novel antifungal antibiotic, is a structural relative of antimycin A
3 (AA) and its mode of action is similar to that of AA which inhibits mitochondrial electron transport at complex III. In spite of their structural resemblance, AA had strong cytotoxicity while UK-2A had little cytotoxicity against LLC-PK1 cells as well as other types of cultured cells. When cells were treated with UK-2A or with A A the intracellular ATP content decreased significantly within 5 minutes in glucose-free medium to almost the same extent in both cases. Moreover, under the same conditions, UK-2A killed cells at a similar rate to AA. This suggested that UK-2A entered into the cells and, like AA, inhibited mitochondrial electron transport. On the other hand, AA stimulated reactive oxygen species (ROS) production within 5 minutes even at a low concentration of 1 μM whereas UK-2A did not show such an effect. The difference in the ROS-producing abilities of UK-2A and AA may account for the different cytotoxic effects of the two compounds.
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NOBUO HOSOKAWA, SHINOBU YAMAMOTO, YOSHIMASA UEHARA, MAKOTO HORI, KAYOK ...
1999 Volume 52 Issue 5 Pages
485-490
Published: May 25, 1999
Released on J-STAGE: September 19, 2008
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Thiazinotrienomycin B (TT-B), an ansamycin isolated from fermentation broths of
Streptomyces sp. MJ672-m3, inhibited the growth
in vitro of human stomach tumor SC-6 cells over 10 times more strongly than the growth of other human tumor cells, such as HeLa (cervix), T24 (bladder) and LX-1 (lung). The extent of growth inhibition by TT-B of SC-6, but not of LX-1 nor T24, was lowered in a competitive manner by raising serum concentrations in the culture medium. TT-B inhibited the cell cycle progression of SC-6 at an early stage of the progression from GO/G1 to S. The inhibition was again competitive with serum concentrations in the culture medium. No direct inhibition of DNA synthesis was observed at the concentration range which caused the cell cycle arrest. TT-B and anti-epidermal growth factor receptor (anti-EGFR) were antagonistic to each other in inhibiting the cell cycle progression of SC-6 from G0/G1 to S, suggesting that the two compounds share the same target, EGFR. The kinase activity of EGFR was little inhibited by TT-B in a cell-free system.
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MASAYASU KASAI, SATORU HATANO, MEIKO KITAGAWA, AKIHISA YOSHIMI, HIROAK ...
1999 Volume 52 Issue 5 Pages
491-500
Published: May 25, 1999
Released on J-STAGE: September 19, 2008
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To improve the oral absorption of ceftizoxime (CZX), 7β-[(
Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acid, we synthesized and evaluated a novel series of bifunctional prodrugs, in which L-alanine was introduced into the aminothiazole-oxime moiety at the C-7 position of the various lipophilic esters of CZX. Among these prodrugs, pivaloyloxymethyl 7β[(
Z)-2-(2-(
S)-alanylaminothiazol-4-yl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylate hydrochloride (ceftizoxime alapivoxil, AS-924) was well absorbed after oral administration in experimental animals and showed potent therapeutic effects in mice infected with Gram-positive and Gram-negative bacteria.
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AKIKO FUKAMI, YOSUKE TANIGUCHI, TOMONORI NAKAMURA, MUN-CHUAL RHO, KANA ...
1999 Volume 52 Issue 5 Pages
501-504
Published: May 25, 1999
Released on J-STAGE: September 19, 2008
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NOBUAKI TSUGE, KEIKO FURIHATA, KAZUO SHIN-YA, YOICHI HAYAKAWA, HARUO S ...
1999 Volume 52 Issue 5 Pages
505-507
Published: May 25, 1999
Released on J-STAGE: September 19, 2008
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TAKAKO SAKURAI, NAOWARAT CHEEPTHAM, TAKASHI MIKAWA, ATSUSHI YOKOTA, FU ...
1999 Volume 52 Issue 5 Pages
508-511
Published: May 25, 1999
Released on J-STAGE: September 19, 2008
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