NH2-terminal pentapeptide of endothelial interleukin 8 is responsible for the induction of apoptosis in leukemic cells and has an antitumor effect in vivo.
We have reported that endothelial interleukin 8 (IL-8) induces apoptosis in leukemic cells in vitro and in vivo, and that interaction between endothelial cells and leukemic cells causes induction of apoptosis through the release of endothelial IL-8 (Y. Terui et al., Biochem. Biophys. Res. Commun., 243: 407-411, 1998; Y. Terui et al., Blood, 92: 2672-2680, 1998). Here, we examined whether a pentapeptide corresponding to the NH2-terminal region of endothelial IL-8 can induce apoptosis in leukemic cells. The NH2-terminal pentapeptide Ala-Val-Leu-Pro-Arg (AVLPR) was found to significantly induce apoptosis in the leukemic cell lines K562, HL-60, Jurkat, and Daudi, as compared with the COOH-terminal pentapeptide Arg-Glu-Ala-Asn-Ser (REANS). Moreover, the NH2-terminal pentapeptide AVLPR significantly inhibited growth of i.p. and s.c. tumor masses of K562 cells and induced apoptosis in these cells in vivo. The active site of endothelial IL-8 is the NH2-terminal pentapeptide AVLPR, and this may serve as a new therapy for hematological malignancies.
Terui
Y
Y
Department of Hematology, Jichi Medical School, Tochigi, Japan.
Tomizuka
H
H
Mishima
Y
Y
Ikeda
M
M
Kasahara
T
T
Uwai
M
M
Mori
M
M
Itoh
T
T
Tanaka
M
M
Yamada
M
M
Shimamura
S
S
Ishizaka
Y
Y
Ozawa
K
K
Hatake
K
K
D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020287:In Situ Nick-End Labeling; D016209:Interleukin-8 / Q000737:chemistry*; D020014:K562 Cells / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016209:Interleukin-8; D009842:Oligopeptides; D010446:Peptide Fragments; C401310:alanyl-valyl-leucyl-prolyl-arginine