Synergistic Anti-Leukemic Effect of Protein Kinase A Activator and PPARγ Agonist Is Independent of Bcl-2 Status.

作者: Bjarte S. Erikstein , Karl J. Tronstad , Emmet McCormack , Frank Schwede , Rolf Bergen

DOI: 10.1182/BLOOD.V110.11.4200.4200

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摘要: The fatty acid derivate tetradecylthioacetic (TTA) and 8-CPT-cAMP have previously been shown to anti-proliferative activities through activation of PPARγ effects on the mitochondrial metabolism, respectively. Based our previous work, we hypothesized that these two agents a converging point action. combined effect compounds was investigated in acute myelogenous cell lines (IPC-81 HL-60), including IPC-81 clones over expressing either Bcl-2 or inducible cAMP early transcription repressors (ICER). Brown Norwegian rat leukaemia (BNML) used as an vivo model system. 8-CPT-cAMP- TTAs anti-leukemic activity assessed vitro. were able synergistically induce decrease viability promyelocytic cells when measured by combinational index. Enforced expression ICER could partially protect from TTA induced apoptosis. did not prevent additive apoptosis induction compounds. An proliferation inhibition detected HL-60 at concentration affect itself. had spleen anti-leukaemic but schedule administration will be further investigated. In conclusion there seems action since they vitro leukemic cells.

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