Reference : Hydroxycoumarin OT-55 kills CML cells alone or in synergy with imatinib or Synribo: I...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Hydroxycoumarin OT-55 kills CML cells alone or in synergy with imatinib or Synribo: Involvement of ER stress and DAMP release
Mazumder, A []
Lee, JY []
Talhi, O []
Cerella []
Chateauvieux, S []
Gaigneaux, Anthoula mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Hong, CR []
Kang, HJ []
Lee, Y []
Kim, KW []
Kim, DW []
Shin, HY []
Dicato, M []
Bachari, K []
Silva, AMS []
Orlikova-Boyer []
Diederich, M []
Cancer Letters
Yes (verified by ORBilu)
[en] We synthetized and investigated the anti-leukemic potential of the novel cytostatic bis(4-hydroxycoumarin) derivative OT-55 which complied with the Lipinski's rule of 5 and induced differential toxicity in various chronic myeloid leukemia (CML) cell models. OT-55 triggered ER stress leading to canonical, caspase-dependent apoptosis and release of danger associated molecular patterns. Consequently, OT-55 promoted phagocytosis of OT-55-treated CML cells by both murine and human monocyte-derived macrophages. Moreover, OT-55 inhibited tumor necrosis factor α-induced activation of nuclear factor-кB and produced synergistic effects when used in combination with imatinib to inhibit colony formation in vitro and Bcr-Abl+ patient blast xenograft growth in zebrafish. Furthermore, OT-55 synergized with omacetaxine in imatinib-resistant KBM-5 R cells to inhibit the expression of Mcl-1, triggering apoptosis. In imatinib-resistant K562 R cells, OT-55 triggered necrosis and blocked tumor formation in zebrafish in combination with omacetaxine.

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