Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
5-azacytidine modulates the response of sensitive and multidrug-resistant K562 leukemic cells to cytostatic drugs
Autore:
Efferth, T; Futscher, BW; Osieka, R;
Indirizzi:
Rhein Westfal TH Aachen, Rhein Westfal TH Aachen, Med Klin 4, Aachen, Germany Rhein Westfal TH Aachen Aachen Germany hen, Med Klin 4, Aachen, Germany Arizona Canc Ctr, Tucson, AZ USA Arizona Canc Ctr Tucson AZ USAArizona Canc Ctr, Tucson, AZ USA
Titolo Testata:
BLOOD CELLS MOLECULES AND DISEASES
fascicolo: 3, volume: 27, anno: 2001,
pagine: 637 - 648
SICI:
1079-9796(200105/06)27:3<637:5MTROS>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
CHRONIC MYELOGENOUS LEUKEMIA; POLYMERASE CHAIN-REACTION; TUMOR-SUPPRESSOR GENE; DNA METHYLATION; CPG ISLAND; MESSENGER-RNA; MDR1 GENE; CISPLATIN; THERAPY; DECITABINE;
Keywords:
bisulfite sequencing; HpaII-sensitive PCR; PCR stop assay;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Efferth, T Virtual Campus Rhineland Palatinate,POB 4380, D-55033 Mainz, Germany Virtual Campus Rhineland Palatinate,POB 4380 Mainz Germany D-55033
Citazione:
T. Efferth et al., "5-azacytidine modulates the response of sensitive and multidrug-resistant K562 leukemic cells to cytostatic drugs", BL CELL M D, 27(3), 2001, pp. 637-648

Abstract

In an endeavor to improve responsiveness of tumor cells to drug combination treatments, we analyzed the effect of 5-azacytidine (5AC) as a model compound for a new class of drugs, DNA-demethylating agents. We used parental K562/WT chronic myelogenous leukemia cells and a multidrug-resistant sublinethereof, K562/ADM. Multidrug-resistant cells were more resistant to daunorubicin, but more sensitive to cisplatin than parental K562 cells as measured by growth inhibition and apoptosis assays. Resistance to daunorubicin canbe explained by amplification of the MDR1 drug transporter gene. Cisplatininduced more DNA damage in specific genes and in the entire genome of K562/ADM cells compared to K562/WT cells using PCR stop assays and atomic absorption spectroscopy. Pretreatment with 5AC modulated the response of K562/ADM cells toward MDR-type drugs (daunorubicin, vincristine, etoposide) and reduced function and expression of MDR1 as analyzed by flow cytometry and RT-PCR. Analysis of CpG island methylation in the promotor region of the MDR1 gene by bisulfite sequencing and a methylation-sensitive HpaII-digestion/PCR approach revealed that methylation of the MDR1 promotor of K562/ADM cellswas greater than in K562/WT cells. 5AC treatment completely abolished MDR1promotor methylation. The unexpected observation that DNA demethylation by5AC rather decreases than increases MDR1 expression in K5612/ADM cells points to still unexplored sequences in the MDR1 promotor whose transcriptional activity may be affected by the methylation status. 5AC pretreatment alsomodulated K562/WT and K562/ADM cells to non-MDR-type drugs such as cisplatin and increased cisplatin-induced DNA damage. (C) 2001 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 11/07/20 alle ore 18:50:38