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 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 (1-300muM) 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.
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China.
You-Li
YL
Zhao
Yan
Y
Tao
Cai-Yun
CY
Fu
Zi-Qing
ZQ
Kong
Qiang
Q
Chen
Rui
R
Wang
D001549:Benzamides / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D064729:Neurokinin-1 Receptor Antagonists; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D015320:Tachykinins / Q000494:pharmacology*
D001549:Benzamides; D064729:Neurokinin-1 Receptor Antagonists; D018377:Neurotransmitter Agents; D010880:Piperidines; D011812:Quinuclidines; D018041:Receptors, Neurokinin-2; D015320:Tachykinins; C507968:hemokinin-1; C085215:SR 140333; C073839:SR 48968