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Titolo:
Suppression of GST-P by treatment with glutathione-doxorubicin conjugate induces potent apoptosis in rat hepatoma cells
Autore:
Asakura, T; Hashizume, Y; Tashiro, K; Searashi, Y; Ohkawa, K; Nishihira, J; Sakai, M; Shibasaki, T;
Indirizzi:
Jikei Univ, Sch Med, Dept Biochem 1, Minato Ku, Tokyo 1058461, Japan JikeiUniv Tokyo Japan 1058461 iochem 1, Minato Ku, Tokyo 1058461, Japan Jikei Univ, Sch Med, Dept Surg, Tokyo, Japan Jikei Univ Tokyo JapanJikei Univ, Sch Med, Dept Surg, Tokyo, Japan Jikei Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, Tokyo, Japan Jikei Univ Tokyo Japan l Med, Div Gastroenterol & Hepatol, Tokyo, Japan Hokkaido Univ, Dept Biochem, Sapporo, Hokkaido, Japan Hokkaido Univ Sapporo Hokkaido Japan t Biochem, Sapporo, Hokkaido, Japan Hokkaido Univ, Grad Sch Med, Sapporo, Hokkaido, Japan Hokkaido Univ Sapporo Hokkaido Japan d Sch Med, Sapporo, Hokkaido, Japan Jikei Univ, Sch Med, Dept Renal Hypertens, Tokyo, Japan Jikei Univ TokyoJapan niv, Sch Med, Dept Renal Hypertens, Tokyo, Japan Kyoritsu Coll Pharmaceut Sci, Dept Pharmaceut Therapeut, Tokyo, Japan Kyoritsu Coll Pharmaceut Sci Tokyo Japan maceut Therapeut, Tokyo, Japan
Titolo Testata:
INTERNATIONAL JOURNAL OF CANCER
fascicolo: 2, volume: 94, anno: 2001,
pagine: 171 - 177
SICI:
0020-7136(20011015)94:2<171:SOGBTW>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
BREAST CANCER-CELLS; S-TRANSFERASE-P; MULTIDRUG-RESISTANCE; DRUG-RESISTANT; CYTO-TOXICITY; ETHACRYNIC-ACID; ADRIAMYCIN; LINES; INHIBITION; OVEREXPRESSION;
Keywords:
doxorubicin; glutathione-doxorubicin conjugate; glutathione S-transferase-P; apoptosis; DNA fragmentation; caspase-3; rat hepatoma cell;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Asakura, T Jikei Univ, Sch Med, Dept Biochem 1, Minato Ku, 3-25-8 Nishi Shinbashi, Tokyo 1058461, Japan Jikei Univ 3-25-8 Nishi Shinbashi Tokyo Japan 1058461 1, Japan
Citazione:
T. Asakura et al., "Suppression of GST-P by treatment with glutathione-doxorubicin conjugate induces potent apoptosis in rat hepatoma cells", INT J CANC, 94(2), 2001, pp. 171-177

Abstract

A conjugate of doxorubicin and glutathione via glutaraldehyde (GSH-DXR) inhibited glutathione S-transferase (GST) activity of rat hepatoma AH66 cells, and treatment of the cells with GSH-DXR induced caspase-3 activation and DNA fragmentation. After treatment of AH66 cells with 0.1 muM GSH-DXR, GST-P (placental type of rat GST isozymes) mRNA and its protein increased transiently and then decreased thereafter compared with the levels in nontreatedcells. Caspase-3 activation and DNA fragmentation were induced following the suppression of GST-P expression by treatment with GSH-DXR. When the cells were treated with 100 muM ethacrynic acid (ECA), an inhibitor of GST, DNAfragmentation and caspase-3 activation were observed. In contrast, treatment of AH66 cells with a low concentration of ECA (1 muM) that showed littleinhibition of GST activity induced slight, but significantly enhanced expression and activity of GST-P, and consequent prevention of DXR- and GSH-DXR-induced DNA fragmentation. Overexpression of GST-pi (placental type of human GST isozymes) by transfection of GST-pi sense cDNA into AH66 cells decreased sensitivities to DXR and GSH-DXR, and the suppression of GST-P by transfection of the antisense cDNA into the cells increased drug sensitivity. On the other hand, there was little change in drug sensitivity caused by overexpression of site-directedly mutated GST-P in which the active-site residue Tyr39 was replaced with His (W39H) or the substrate-binding site residueCys48 was replaced with Ser (C48S) by transfection of those cDNAs into AH66 cells. These results suggested that the suppression of GST-P in AH66 cells treated with GSH-DXR must play an important role in the induction of apoptosis. (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 11:34:46