Identification of molecular targets for selective elimination of TRAIL-resistant leukemia cells. From spots to in vitro assays using TOP15 charts
Jazyk angličtina Země Německo Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
19834905
DOI
10.1002/pmic.200900335
Knihovny.cz E-zdroje
- MeSH
- 2D gelová elektroforéza MeSH
- antitumorózní látky farmakologie MeSH
- apoptóza účinky léků MeSH
- chemorezistence * MeSH
- DNA vazebné proteiny metabolismus MeSH
- HL-60 buňky MeSH
- jaderné proteiny metabolismus MeSH
- leukemie metabolismus MeSH
- lidé MeSH
- MCM komplex, komponenta 7 MeSH
- protein TRAIL farmakologie MeSH
- proteiny buněčného cyklu metabolismus MeSH
- regulace genové exprese u nádorů účinky léků MeSH
- replikační protein A metabolismus MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
- western blotting MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antitumorózní látky MeSH
- DNA vazebné proteiny MeSH
- jaderné proteiny MeSH
- MCM komplex, komponenta 7 MeSH
- MCM7 protein, human MeSH Prohlížeč
- protein TRAIL MeSH
- proteiny buněčného cyklu MeSH
- replikační protein A MeSH
- RPA2 protein, human MeSH Prohlížeč
The resistance of malignant cells to chemotherapy calls for the development of novel anti-cancer drugs. TNF-related apoptosis-inducing ligand (TRAIL) is a pro-apoptotic cytokine, which selectively induces apoptosis in malignant cells. We derived two TRAIL-resistant HL-60 subclones, HL-60/P1 and HL-60/P2, from a TRAIL-sensitive HL-60 acute promyelocytic leukemia cell line. To identify therapeutically exploitable "weaknesses" of the TRAIL-resistant leukemia cells that could be used as molecular targets for their elimination, we performed proteomic (2-DE) analysis and compared both TRAIL-resistant subclones with the original TRAIL-sensitive HL-60 cells. We identified over 40 differentially expressed proteins. To significantly narrow the lists of candidate proteins, we excluded proteins that are known to be often differentially expressed, regardless of experiment type and tissue (the so-called "TOP15" proteins). Decreased expression of DNA replication and maintenance proteins MCM7 and RPA32 in HL-60/P1 cells, and the marked down-regulation of enzyme adenosine deaminase in HL-60/P2 cells, suggests increased sensitivity of these cells to DNA-interfering drugs, and adenosine and its homologues, respectively. In a series of in vitro assays, we confirmed the increased toxicity of etoposide and cisplatin to TRAIL resistant HL-60/P1 cells, and adenosine and vidarabine to HL-60/P2, compared with TRAIL-sensitive HL-60 cells.
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