Granulocyte Differentiation Inducer, Hexapeptide HLDF-6, Decreases Cytotoxic Effect of Tumor Necrosis Factor on HL-60 Cell Line

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N. V. Gibanova, T. V. Rakitina, V. M. Lipkin, and I. A. Kostanyan^*

Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997 Moscow, Russia; fax: (495) 336-6166; E-mail: iakost@mail.ibch.ru

^* To whom correspondence should be addressed.

Received June 27, 2006; Revision received August 29, 2006

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The effect of hexapeptide HLDF-6, the granulocytic differentiation inducer, on the tumor necrosis factor alpha (TNF-alpha)-induced differentiation and apoptosis of human promyelocytic leukemia HL-60 cells has been investigated. Costimulation of HL-60 cells with HLDF-6 and TNF-alpha enhanced granulocyte differentiation, whereas the level of monocyte differentiation remained unchanged; however, the cytotoxic action of TNF-alpha on these cells decreased. The protective effect of HLDF-6 peptide did not depend on activation of NF-kappaB (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-alpha-mediated activation of caspase-3, we have proposed the hypothesis that HLDF-6 increases resistance of HL-60 cells to the TNF-alpha cytotoxic effect due to inhibition of some stages of mitochondria-dependent apoptotic signaling.

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KEY WORDS: cell differentiation, apoptosis, peptide HLDF-6, TNF-alpha, HL-60 cell line, transcription factor NF-kappaB, ceramide

DOI: 10.1134/S0006297907010063

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