• Medientyp: E-Artikel
  • Titel: IFN-β Pretreatment Sensitizes Human Melanoma Cells to TRAIL/Apo2 Ligand-Induced Apoptosis
  • Beteiligte: Chawla-Sarkar, Mamta; Leaman, Douglas W.; Jacobs, Barbara S.; Borden, Ernest C.
  • Erschienen: The American Association of Immunologists, 2002
  • Erschienen in: The Journal of Immunology
  • Umfang: 847-855
  • Sprache: Englisch
  • DOI: 10.4049/jimmunol.169.2.847
  • ISSN: 0022-1767; 1550-6606
  • Schlagwörter: Immunology ; Immunology and Allergy
  • Zusammenfassung: <jats:title>Abstract</jats:title> <jats:p>All human melanoma cell lines (assessed by annexin V and TUNEL assays) were resistant to apoptosis induction by TRAIL/Apo2L protein. TRAIL/Apo2L activated caspase-8 and caspase-3, but subsequent apoptotic events such as poly(ADP-ribose) polymerase cleavage and DNA fragmentation were not observed. To probe the molecular mechanisms of cellular resistance to apoptosis, melanoma cell lines were analyzed for expression of apoptosis regulators (apoptotic protease-associated factor-1, FLIP, caspase-8, caspase-9, caspase-3, cellular inhibitor of apoptosis, Bcl-2, or Bax); no correlation was observed. TRAIL/Apo2L was induced in melanoma cell lines by IFN-β and had been correlated with apoptosis induction. Because IFN-β induced other gene products that have been associated with apoptosis, it was postulated that one or more IFN-stimulated genes might sensitize cells to TRAIL/Apo2L. Melanoma cell lines were treated with IFN-β for 16–24 h before treatment with TRAIL/Apo2L. Regardless of their sensitivity to either cytokine alone, &amp;gt;30% of cells underwent apoptosis in response to the combined treatment. Induction of apoptosis by IFN-β and TRAIL/Apo2L in combination correlated with synergistic activation of caspase-9, a decrease in mitochondrial potential, and cleavage of poly(ADP-ribose) polymerase. Cleavage of X-linked inhibitor of apoptosis following IFN-β and TRAIL/Apo2L treatment was observed in sensitive WM9, A375, or WM3211 cells but not in resistant WM35 or WM164 cells. Thus, in vitro IFN-β and TRAIL/Apo2L combination treatment had more potent apoptotic and anti-growth effects when compared with either cytokine alone in melanoma cells lines.</jats:p>
  • Beschreibung: <jats:title>Abstract</jats:title>
    <jats:p>All human melanoma cell lines (assessed by annexin V and TUNEL assays) were resistant to apoptosis induction by TRAIL/Apo2L protein. TRAIL/Apo2L activated caspase-8 and caspase-3, but subsequent apoptotic events such as poly(ADP-ribose) polymerase cleavage and DNA fragmentation were not observed. To probe the molecular mechanisms of cellular resistance to apoptosis, melanoma cell lines were analyzed for expression of apoptosis regulators (apoptotic protease-associated factor-1, FLIP, caspase-8, caspase-9, caspase-3, cellular inhibitor of apoptosis, Bcl-2, or Bax); no correlation was observed. TRAIL/Apo2L was induced in melanoma cell lines by IFN-β and had been correlated with apoptosis induction. Because IFN-β induced other gene products that have been associated with apoptosis, it was postulated that one or more IFN-stimulated genes might sensitize cells to TRAIL/Apo2L. Melanoma cell lines were treated with IFN-β for 16–24 h before treatment with TRAIL/Apo2L. Regardless of their sensitivity to either cytokine alone, &amp;gt;30% of cells underwent apoptosis in response to the combined treatment. Induction of apoptosis by IFN-β and TRAIL/Apo2L in combination correlated with synergistic activation of caspase-9, a decrease in mitochondrial potential, and cleavage of poly(ADP-ribose) polymerase. Cleavage of X-linked inhibitor of apoptosis following IFN-β and TRAIL/Apo2L treatment was observed in sensitive WM9, A375, or WM3211 cells but not in resistant WM35 or WM164 cells. Thus, in vitro IFN-β and TRAIL/Apo2L combination treatment had more potent apoptotic and anti-growth effects when compared with either cytokine alone in melanoma cells lines.</jats:p>
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  • Zugangsstatus: Freier Zugang