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Titolo:
Subcellular redistribution of BAX during apoptosis induced by anticancer drugs
Autore:
Godlewski, MM; Motyl, MA; Gajkowska, B; Wareski, P; Koronkiewicz, M; Motyl, T;
Indirizzi:
Agr Univ Warsaw, Fac Vet Med, Dept Physiol Biochem Pharmacol & Toxicol, PL-02787 Warsaw, Poland Agr Univ Warsaw Warsaw Poland PL-02787 Toxicol, PL-02787 Warsaw, Poland Med Univ, Dept Pharmacokinet, PL-00927 Warsaw, Poland Med Univ Warsaw Poland PL-00927 t Pharmacokinet, PL-00927 Warsaw, Poland Polish Acad Sci, Med Res Ctr, Lab Cell Ultrastruct, PL-02106 Warsaw, Poland Polish Acad Sci Warsaw Poland PL-02106 rastruct, PL-02106 Warsaw, Poland Drug Inst, Flow Cytometry Lab, PL-00750 Warsaw, Poland Drug Inst Warsaw Poland PL-00750 Cytometry Lab, PL-00750 Warsaw, Poland
Titolo Testata:
ANTI-CANCER DRUGS
fascicolo: 7, volume: 12, anno: 2001,
pagine: 607 - 617
SICI:
0959-4973(200108)12:7<607:SROBDA>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
MAMMARY EPITHELIAL-CELLS; CYTOCHROME-C RELEASE; BCL-X-L; NUCLEAR MATRIX; MITOCHONDRIA; EXPRESSION; PROTEINS; CHANNEL; CANCER; TRANSLOCATION;
Keywords:
anticancer drugs; apoptosis; BAX; laser scanning cytometry; nimesulide;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Motyl, T Agr Univ Warsaw, Fac Vet Med, Dept Physiol Biochem Pharmacol & Toxicol, Nowoursynowska 166, PL-02787 Warsaw, Poland Agr Univ Warsaw Nowoursynowska 166 Warsaw Poland PL-02787 Poland
Citazione:
M.M. Godlewski et al., "Subcellular redistribution of BAX during apoptosis induced by anticancer drugs", ANTI-CANC D, 12(7), 2001, pp. 607-617

Abstract

BAX is the 192-amino acid, 21-kDa protein which is ubiquitously distributed in normal tissues and is regarded as a tumor suppressor sensitizing malignant cells to anticancer drugs. In spite of many studies, the molecular mechanism of BAX action is still obscure. In the present study subcellular BAXtranslocations in human colon adenocarcinoma COLO 205 cells exposed to various anticancer drugs [camptothecin (CPT), etoposide (ETO), staurosporine (STP), 2-chloro-2'-deoxyadenosine (2CdA) and nimesulide (NIM)] was examined. Cells were grown on coverslips under optimal conditions (10% FCS/DMEM) or were stimulated to apoptosis with the drugs examined. Laser scanning cytometry was applied for the quantitative analysis of BAX expression, and distribution in the cytoplasmic (BAX Cf) and nuclear (BAX Nf) area. BAX maximal pixel (BAX MP), the parameter corresponding to aggregation of BAX in the cell, was also measured. All examined drugs increased the number of cells withhigh BAX MP, reaching the peak at 60 min after drug administration. The most pronounced effect was In the case of 2CdA, CPT and STP. The increase In BAX MP was observed only when antibody recognizing the 43-61 amino acid sequence was used. When antibody binding the N-terminal epitope (11-30 amino acid sequence) was applied, the number of cells expressing high BAX MP significantly decreased. These results Indicate that apoptotic stimuli deliveredby anticancer drugs led to aggregation of BAX In cancer cells, which is dependent on BAX activation by Its cleavage at the N-terminal epitope and exposure of the BH3 domain. It was shown that BAX Nf increased in cells treated with CPT, STP, ETO, 2CdA and NIM, whereas BAX Cf rose after STP and NIM. The increase in BAX Nf and, occurring in most treatments, the increase in the BAX Nf:Cf ratio indicates a BAX shift from the cytoplasm to the nucleus. Furthermore, staining with different antibodies showed that only the activated form of BAX was translocated to the nucleus. Immunoelectron microscopyrevealed that CPT-induced apoptosis was associated with translocation of BAX from the cytosol to organellar membranes (mitochondrial, Golgi apparatusand endoplasmic reticulum) and via nuclear envelope pores to the nucleus, occurring within 60-180 min of cell exposure to the drug. The subcellular translocations of BAX preceded in time the appearance of morphological symptoms of apoptosis. In conclusion, (I) in spite of different molecular mechanisms of apoptosis induction by the anticancer drugs examined, BAX remains acommon link in the chain of reactions leading to cell death, and (ii) BAX activation and subcellular translocations from the cytosol to organellar membranes and nucleus are key cellular responses to drugs bearing proapoptotic properties. [(C) 2001 Lippincott Williams & Wilkins.].

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/05/20 alle ore 13:35:03