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Titolo:
Inhibition of proteasome function induced apoptosis in gastric cancer
Autore:
Fan, XM; Wong, BCY; Wang, WP; Zhou, XM; Cho, CH; Yuen, ST; Leung, SY; Lin, MCM; Kung, HF; Lam, SK;
Indirizzi:
Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China Univ Hong Kong Hong Kong Hong Kong Peoples R China Kong, Peoples R China Fourth Mil Med Univ, Xijing Hosp, Inst Digest Dis, Xian 710032, Peoples R China Fourth Mil Med Univ Xian Peoples R China 710032 710032, Peoples R China Univ Hong Kong, Dept Pharmacol, Hong Kong, Hong Kong, Peoples R China UnivHong Kong Hong Kong Hong Kong Peoples R China Kong, Peoples R China Univ Hong Kong, Dept Pathol, Hong Kong, Hong Kong, Peoples R China Univ Hong Kong Hong Kong Hong Kong Peoples R China Kong, Peoples R China Univ Hong Kong, Inst Mol Biol, Hong Kong, Hong Kong, Peoples R China Univ Hong Kong Hong Kong Hong Kong Peoples R China Kong, Peoples R China
Titolo Testata:
INTERNATIONAL JOURNAL OF CANCER
fascicolo: 4, volume: 93, anno: 2001,
pagine: 481 - 488
SICI:
0020-7136(20010815)93:4<481:IOPFIA>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
CYTOCHROME-C RELEASE; CELL-DEATH; CASPASE ACTIVATION; P53; INDUCTION; PATHWAY; MITOCHONDRIA; P27; BAX; DEGRADATION;
Keywords:
apoptosis; gastric cancer; ubiquitin-proteasome; caspases; bax;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Wong, BCY Univ Hong Kong, Queen Mary Hosp, Dept Med, Hong Kong, Hong Kong,Peoples RChina Univ Hong Kong Hong Kong Hong Kong Peoples R China ples RChina
Citazione:
X.M. Fan et al., "Inhibition of proteasome function induced apoptosis in gastric cancer", INT J CANC, 93(4), 2001, pp. 481-488

Abstract

The ubiquitin-proteasome pathway plays a critical role in the degradation of cellular proteins and cell cycle control. Dysregulating the degradation of such proteins should have profound effects on tumor growth and causes cells to undergo apoptosis, The aims of this study are to evaluate the ubiquitin-proteasome pathway in gastric cancer and the potential role of pharmacological inhibition of proteasome on induction of apoptosis in gastric cancer cells. Gastric cancer cell lines ACS (p53 wild-type) and MKN-28 (p53 mutant) were treated with proteasome inhibitor MG132, The results showed that MG132 inhibited cell proliferation in AGS and MKN-28 cells in a time- and dose-dependent manner. The inhibition of cell proliferation was caused by apoptosis which was also time- and dose-dependent.. ACS cells were more responsive to MG132 than MKN-28 cells. Induction of apoptosis was preceded by theactivation of caspase-3, as measured by a colorimetric caspase-3 cellular activity and Western blotting of the cleavage of caspase-3 and its substrate PARP, Activation of caspase-7 was also exhibited. In addition, z-VAD-fmk,a broad spectrum caspase inhibitor, reversed apoptosis induced by MG132 inAGS and MKN28 cells. Although z-DEVD-fmk, a specific caspase-3 inhibitor, suppressed MG132-induced apoptosis in MKN28 cells, it only partially rescued the apoptotic effect in AGS cells. Caspase-3 activation was the result ofrelease of cytochrome c from mitochondria into the cytosol, as a consequence of upregulation of bax. There were overexpressions of all the proteasome-related proteins p53 p21(waf1) and p27(kip1) at 4 h, after proteasome inhibition which was identified by the accumulation of ubiquitin-tagged proteins, This was accompanied by accumulation of cells at G(1) phase. Our presentstudy suggests that inhibition of proteasome function in gastric cancer cells induces apoptosis and proteasomal inhibitors have potential use as novel anticancer drugs in gastric cancer, (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 01:20:50