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Titolo:
Effect of the proteasome inhibitor ALLnL on cisplatin sensitivity in humanovarian tumor cells
Autore:
Yunmbam, MK; Li, QDQ; Mimnaugh, EG; Kayastha, GL; Yu, JJ; Jones, LN; Neckers, L; Reed, E;
Indirizzi:
NCI, Med Ovarian Canc Sect, Dev Therapeut Dept, NIH, Bethesda, MD 20892 USA NCI Bethesda MD USA 20892 Dev Therapeut Dept, NIH, Bethesda, MD 20892 USA NCI, Tumor Cell Biol Sect, Cell & Canc Biol Dept, Med Branch,Div Clin Sci,NIH, Bethesda, MD 20892 USA NCI Bethesda MD USA 20892 Branch,Div Clin Sci,NIH, Bethesda, MD 20892 USA
Titolo Testata:
INTERNATIONAL JOURNAL OF ONCOLOGY
fascicolo: 4, volume: 19, anno: 2001,
pagine: 741 - 748
SICI:
1019-6439(200110)19:4<741:EOTPIA>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
DNA ADDUCT FORMATION; REPAIR GENE RAD6; EXCISION-REPAIR; CANCER CELLS; DRUG ACCUMULATION; RNA EXPRESSION; RESISTANCE; APOPTOSIS; PLATINUM; LINES;
Keywords:
proteasome inhibitor; ALLnL; cisplatin; DNA repair; ovarian cancer;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Reed, E W Virginia Univ, Hlth Sci Ctr, Mary Babb Randolph Canc Ctr, POB 9300, Morgantown, WV 26506 USA W Virginia Univ POB 9300 Morgantown WV USA 26506 own, WV 26506 USA
Citazione:
M.K. Yunmbam et al., "Effect of the proteasome inhibitor ALLnL on cisplatin sensitivity in humanovarian tumor cells", INT J ONCOL, 19(4), 2001, pp. 741-748

Abstract

Small molecules suppressing proteasome function inhibit the post-translational ubiquitination of selected proteins. Ubiquitin H2A is an example of anabundant chromatin-associated protein that is known to be ubiquitinated, which is important for several proteins involved in the repair of DNA damage. We therefore studied the effect of the proteasome inhibitor, N-acetyl leucyl-leucyl norlucinal (ALLnL), on cisplatin sensitivity in three human ovarian tumor cell lines. The proteasome inhibitor ALLnL was administered for 4h before cells were subsequently exposed to cisplatin for 1 h. Our resultsshowed that ALLnL, at its respective IC, concentration, increased cellularsensitivity to cisplatin in an additive manner in human ovarian cancer A2780, A2780/CP70, and OVCAR3 cells. We also demonstrated that ALLnL caused a 50% increase in total cellular accumulation of cisplatin, and reduced the rate of cisplatin efflux by about 50%. In addition, DNA damage levels were increased after ALLnL treatment. By contrast, DNA repair was inhibited 2 to 3-fold in ALLnL-pretreated cells, as compared to the controls. Furthermore,our study showed that ALLnL deubiquitinated nucleosomal histone H2A in these cells in a concentration-dependent fashion, as assessed by Western blot analysis. These data suggest that sublethal levels of exposure to agents that inhibit proteasome function may alter the subcellular pharmacology of platinum in human ovarian carcinoma cells.

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Documento generato il 23/09/18 alle ore 08:41:40