Cell permeable Bcl-2 binding peptides: A chemical approach to apoptosis induction in tumor cells

Bcl-2 is a potent suppressor of apoptosis, and its overexpression contribut es to tumorigenesis in many types of human cancers. To test the possibility of modulating Bcl-2 function as an anticancer strategy, a cell permeable B cl-2 binding peptide, cell permeable moiety (cpm)-1285, was designed by che mically attaching a fatty acid to a peptide derived from the proapoptotic p rotein Bad. cpm-1285 entered HL-60 tumor cells, bound Bcl-2 protein, and in duced apoptosis in vitro. In contrast, cpm-1285 had little effect on normal human peripheral blood lymphocytes. Furthermore, cpm-1285 had in vivo acti vity in slowing human myeloid leukemia growth in severe combined immunodefi cient mice. These results demonstrate a novel approach for therapeutic inte rvention of tumor growth in vivo with small molecule inhibitors of Bcl-2.