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Titolo:
Effect of inhibitors of cysteine and serine proteases in anticancer drug-induced apoptosis in gastric cancer cells
Autore:
Kim, R; Inoue, H; Tanabe, K; Toge, T;
Indirizzi:
Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Surg Oncol, Minami Ku, Hiroshima 7348553, Japan Hiroshima Univ Hiroshima Japan 7348553 nami Ku, Hiroshima 7348553, Japan
Titolo Testata:
INTERNATIONAL JOURNAL OF ONCOLOGY
fascicolo: 6, volume: 18, anno: 2001,
pagine: 1227 - 1232
SICI:
1019-6439(200106)18:6<1227:EOIOCA>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
CYTOCHROME-C RELEASE; HL-60 CELLS; ACTIVATION; DEATH; MITOCHONDRIA; OVEREXPRESSION; FAMILY; AGENTS; P53;
Keywords:
caspase inhibitor; serine protease inhibitor; apoptosis; gastric cancer; anticancer drugs;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Kim, R Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Surg Oncol, MinamiKu, 1-2-3 Kasumi, Hiroshima 7348553, Japan Hiroshima Univ 1-2-3 Kasumi Hiroshima Japan 7348553 7348553, Japan
Citazione:
R. Kim et al., "Effect of inhibitors of cysteine and serine proteases in anticancer drug-induced apoptosis in gastric cancer cells", INT J ONCOL, 18(6), 2001, pp. 1227-1232

Abstract

Activation of proteases can play an important role in apoptotic cell deathinduced by anticancer drugs. To assess involvement of activation of cysteine and serine proteases in anticancer drug-induced apoptosis, we tested effect of inhibitors of cysteine and serine ploteases on sensitivity to anticancer drugs in MKN45 gastric cancer cells. Cytotoxic effect by adriamycin (ADM), SN-38 (active form of irrino-tecan) and cisplatin (CDDP) was significantly prevented by cotreatment with Z-Val-Ala-Asp-fluoromethylketone (Z-VAD-fmk) (p <0.01), a pancaspase inhibitor compared with drug alone using MTT assay. In contrast, cotreatment with N-acetyl-Tyr-Val-Ala-Asp aldehyde (AC-YVAD-CHO), a caspase 1 inhibitor did not prevent any cytotoxic effect of these drugs. Cotreatment of N-acetyl-Asp-Glu-Val-Asp aldehyde (AC-DEVD-CHO), acaspase 3 inhibitor prevented cytotoxic effect of VP-16 and SN-38 (p <0.01). Prevention of these cytotoxic effects by caspase inhibitors was not dose-dependent. Cotreatment of N-tosyl-L-lysyl chloromethylketone (TLCK), a serine protease inhibitor significantly prevented cytotoxic effect of ADM, SN-38, 5-fluorouracil (5-FU) and CDDP in a slight dose-dependent manner (p <0.01) except for etoposide (VP-16) and docetaxel (TXT), while an other serineprotease inhibitor, N-tosyl-L-phenylalanyl chloromethylketone (TPCK) did not prevent any anticancer drug-induced cytotoxic effect. These effects wereassociated with prevention of internucleosomal DNA ladder formation in apoptosis. Further, protease inhibitors did not block induction of cytochrome c, that can explain the partial effect of prevention by anticancer-induced cell death. These results suggest that anticancer drug-induced cytotoxic effect is mediated by activation of serine protease (caspase- independent) aswell as caspase-dependent pathway leading to apoptotic cell death, and that protease-independent pathway may also be involved in apoptotic pathways. The involvement of protease in signal transduction pathways may differ in cytotoxic action of drugs in gastric cancer cells.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/07/20 alle ore 05:22:16