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Human hemokinin-1 and human hemokinin-1(4–11), mammalian tachykinin peptides, suppress proliferation and induce differentiation in HL-60 cells
Human hemokinin-1 (h HK-1) and its truncated form h HK-1(4–11) are mammalian tachykinin peptides encoded by the TAC4 gene identified in human, and the biological functions of these peptides have not been well investigated. The tachykinins have shown immuno-regulatory activities in humans. In the pre...
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Published in: | Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2009-08, Vol.30 (8), p.1514-1522 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Human hemokinin-1 (h HK-1) and its truncated form h HK-1(4–11) are mammalian tachykinin peptides encoded by the
TAC4 gene identified in human, and the biological functions of these peptides have not been well investigated. The tachykinins have shown immuno-regulatory activities in humans. In the present study, we investigated the effects of h HK-1 and h HK-1(4–11) on the proliferation and differentiation of a human promyelocyte leukemia cell line, HL-60. It is noteworthy that h HK-1 (1–300
μM) displayed inhibitory effects on the proliferation of HL-60 cells in a dose- and time-dependent manner. The effect of suppressing proliferation induced by these peptides was accompanied by an accumulation of cell cycle in the S phase. Moreover, this peptide induced differentiation of HL-60 cells by significantly increasing the NBT-reduction activity. The effects induced by h HK-1(4–11) on HL-60 cells were similar to that of h HK-1, indicating that it is the active fragment of h HK-1. However these effects induced by h HK-1 or h HK-1(4–11) were not antagonized by the NK
1 receptor antagonist SR140333 or the NK
2 receptor antagonist SR48968. All the results indicated that h HK-1 and h HK-1(4–11) were able to significantly inhibit proliferation and induce differentiation and S phase arrest of a human promyelocyte leukemia cell line HL-60, which may not be mediated through the activation of classical tachykinin NK
1 receptors and tachykinin NK
2 receptors. Our observations also implied that h HK-1 and h HK-1(4–11) could act as immunomodulatory factors in cancer chemotherapy. |
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ISSN: | 0196-9781 1873-5169 |
DOI: | 10.1016/j.peptides.2009.04.024 |