Lung and
prostate cancers are major health problems worldwide. Treatments with standard
chemotherapy agents are relatively ineffective.
Combination chemotherapy gives better treatment than a single agent because the drugs can inhibit the
cancer in different pathways, but new therapeutic agents are needed for the treatment of both
tumor types.
Bradykinin (BK) antagonists offer advantages of combination
therapy in one compound. These promising multitargeted anti-
cancer compounds selectively stimulate apoptosis in
cancers and also inhibit both angiogenesis and matrix
metalloprotease (
MMP) action in treated lung and prostate
tumors in nude mice. The highly potent, metabolism-resistant
bradykinin antagonist peptide dimer, B-9870 [SUIM-(DArg-
Arg-Pro-
Hyp-Gly-Igl-Ser-DIgl-Oic-Arg)2] (SUIM=suberimidyl; Hyp=
4-hydroxyproline; Igl=alpha-(2-indanyl)
glycine; Oic=octahydroindole-2-
carboxylic acid) and its non-
peptide mimetic,
BKM-570 [2,3,4,5,6-pentafluorocinnamoyl-(o-2,6-dichlorobenzyl)-
L-tyrosine-N-(4-amino-2,2,6,6-tetramethylpiperidyl)
amide] are superior to the widely used but toxic chemotherapeutic drugs
cisplatin and
taxotere. In certain combinations, they act synergistically with standard anti-
cancer drugs. Due to its structure and
biological activity,
BKM-570 is an attractive lead compound for derivatization and evaluation for lung and
prostate cancer drugs.