NH2-terminal pentapeptide of endothelial interleukin 8 is responsible for the induction of apoptosis in leukemic cells and has an antitumor effect invivo

We have reported that endothelial interleukin 8 (IL-8) induces apoptosis in leukemic cells in vitro and in vivo, and that interaction between endothel ial cells and leukemic cells causes induction of apoptosis through the rele ase of endothelial IL-8 (Y, Terui et at, Biochem, Biophys. Res. Commun,, 24 3: 407-411, 1998; Y, Terui et al., Blood, 92: 2672-2680, 1998), Here, we ex amined whether a pentapeptide corresponding to the NH2-terminal region of e ndothelial IL-8 can induce apoptosis in leukemic cells. The NH2-terminal pe ntapeptide Ala-Val-Leu-Pro-Arg (AVLPR) was found to significantly induce ap optosis in the leukemic cell lines K562, HL-60, Jurkat, and Daudi, as compa red with the COOH-terminal pentapeptide Arg-Glu-Ala-Asn-Ser (REANS), Moreov er, the NH2-terminal pentapeptide AVLPR significantly inhibited growth of i .p. and s.c. tumor masses of K562 cells and induced apoptosis in these cell s in vivo. The active site of endothelial IL-8 is the NH2-terminal pentapep tide AVLPR, and this may serve as a new therapy for hematological malignanc ies.