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Titolo:
Interactions between 2-fluoroadenine 9-beta-d-arabinofuranoside and the kinase inhibitor UCN-01 in human leukemia and lymphoma cells
Autore:
Harvey, S; Decker, R; Dal, Y; Schaefer, G; Tang, L; Kramer, L; Dent, P; Grant, S;
Indirizzi:
Virginia Commonwealth Univ, Med Coll Virginia, Dept Med, Richmond, VA 23298 USA Virginia Commonwealth Univ Richmond VA USA 23298 , Richmond, VA 23298 USA Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol, Richmond, VA 23298 USA Virginia Commonwealth Univ Richmond VA USA 23298 , Richmond, VA 23298 USA Virginia Commonwealth Univ, Med Coll Virginia, Dept Microbiol, Richmond, VA 23298 USA Virginia Commonwealth Univ Richmond VA USA 23298 , Richmond, VA 23298 USA Virginia Commonwealth Univ, Med Coll Virginia, Dept Biochem, Richmond, VA 23298 USA Virginia Commonwealth Univ Richmond VA USA 23298 , Richmond, VA 23298 USA Virginia Commonwealth Univ, Med Coll Virginia, Dept Radiat Oncol, Richmond, VA 23298 USA Virginia Commonwealth Univ Richmond VA USA 23298 , Richmond, VA 23298 USA
Titolo Testata:
CLINICAL CANCER RESEARCH
fascicolo: 2, volume: 7, anno: 2001,
pagine: 320 - 330
SICI:
1078-0432(200102)7:2<320:IB29AT>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
CHRONIC LYMPHOCYTIC-LEUKEMIA; PROTEIN-KINASE; SELECTIVE INHIBITOR; FLUDARABINE PHOSPHATE; ANTITUMOR-ACTIVITY; INDUCED APOPTOSIS; ANTICANCER DRUGS; P53; 7-HYDROXYSTAUROSPORINE; CYTOTOXICITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Grant, S Virginia Commonwealth Univ, Med Coll Virginia, Div Hematol Oncol,MCV Stn Box 230, Richmond, VA 23298 USA Virginia Commonwealth Univ MCV StnBox 230 Richmond VA USA 23298
Citazione:
S. Harvey et al., "Interactions between 2-fluoroadenine 9-beta-d-arabinofuranoside and the kinase inhibitor UCN-01 in human leukemia and lymphoma cells", CLIN CANC R, 7(2), 2001, pp. 320-330

Abstract

Interactions between the purine analogue 2-fluoroadenine 9-beta -D-arabinofuranoside (F-ara-A) and the kinase inhibitor UCN-01 have been examined in human leukemia cells (U937 and HL-60) with respect to induction of mitochondrial damage, caspase activation, apoptosis, and loss of clonogenic survival, Simultaneous or subsequent exposure of F-ara-A-treated cells (2 muM) to UCN-01 (100 nM) resulted in a marked potentiation of apoptosis, manifested by loss of mitochondrial membrane potential (Delta psi (m)), cleavage/activation of procaspase-9 and procaspase-3, DNA fragmentation, and degradation of poly-ADP(ribosyl) polymerase, Coadministration of UCN-01 with F-ara-PL was also associated with diminished phosphorylation of the cdc25 phosphatase. In contrast, exposure of cells to the sequence UCN-01, followed by F-ara-A, resulted in only a modest increase in apoptotic cells, The ability of UCN-01 to potentiate F-ara-A-mediated lethality was not mimicked by the selective PKC inhibitor bisindolylmaleimide nor did treatment of cells with UCN-01 enhance formation of F-ara-ATP or increase incorporation of [H-3]F-ara-Ainto DNA. Enhanced apoptosis in cells exposed sequentially or simultaneously to F-ara-A and UCN-01 was accompanied by a substantial reduction in colony formation (e.g., to 0.01% of control values). Cotreatment with UCN-01 also increased F-ara-A-mediated apoptosis and loss of Delta psi (m) in U937 cells ectopically expressing Bcl-2, although not to the same extent as that observed in empty-vector controls, Finally, simultaneous exposure (24 h) ofmalignant B lymphocytes from the pleural effusion of a patient with indolent non-Hodgkin's lymphoma to F-ara-A and UCN-01 ex vivo resulted in a striking increase in apoptosis, as determined by terminal deoxynucleotidyltrans-ferase-mediated nick end labeling assay. These findings indicate that UCN-01 increases F-ara-A-induced mitochondrial damage and apoptosis in human leukemia cells in a sequence-dependent manner, and that these events occur in at least some primary human lymphoma cells.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/07/20 alle ore 01:16:22