Granulocyte differentiation inducer, hexapeptide HLDF-6, decreases cytotoxic effect of tumor necrosis factor on HL-60 cell line

Gibanova, N.; Rakitina, T.; Lipkin, V.; Kostanyan, I.
January 2007
Biochemistry (00062979);Jan2007, Vol. 72 Issue 1, p49
Academic Journal
The effect of hexapeptide HLDF-6, the granulocytic differentiation inducer, on the tumor necrosis factor α (TNF-α)-induced differentiation and apoptosis of human promyelocytic leukemia HL-60 cells has been investigated. Costimulation of HL-60 cells with HLDF-6 and TNF-α enhanced granulocyte differentiation, whereas the level of monocyte differentiation remained unchanged; however, the cytotoxic action of TNF-α on these cells decreased. The protective effect of HLDF-6 peptide did not depend on activation of NF-κB (nuclear transcription factor). Since HLDF-6 peptide decreases the number of cells entering apoptosis caused by C2-ceramide, a mediator of TNF-induced apoptosis, and also reduces TNF-α-mediated activation of caspase-3, we have proposed the hypothesis that HLDF-6 increases resistance of HL-60 cells to the TNF-α cytotoxic effect due to inhibition of some stages of mitochondria-dependent apoptotic signaling.


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