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NH₂-Terminal Pentapeptide of Endothelial Interleukin 8 Is Responsible for the Induction of Apoptosis in Leukemic Cells and Has an Antitumor Effect in Vivo¹

Department of Hematology, Jichi Medical School, Tochigi 329-04, Japan [Y. T., H. T., M. U., M. M., K. O., K. H.]; Biochemical Research Laboratory, Morinaga Milk Industry Co. Ltd., Kanagawa 228, Japan [Y. M., M. I., T. I., M. T., M. Y., S. S.]; Department of Biochemistry, Kyoritsu College of Pharmacy, Tokyo 105, Japan [T. K.]; and Department of Intractable Disease, International Medical Center of Japan, Tokyo, Japan [Y. I.]

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.

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