Targeted destruction of prostate and breast cancers by membrane-disrupting peptides linked to gonadotropic hormones


William H. Hansel1, Carola Leuschner1, and Fred M. Enright2. (1) Reproductive Biotechnology, Pennington Biomedical Research Center, Louisiana State Univ, 6400 Perkins Road, Baton Rouge, LA 70808, (2) Dept. of Veterinary Science, LSU Ag Center, 111 Dalrymple Bldg, Baton Rouge, LA 70803
Prostate and breast cancer cells express receptors for luteinizing hormone (LH or CG) and luteinizing hormone releasing hormone (LHRH). We have conjugated a membrane- disrupting peptide (Hecate or Phor14) to a 15 amino acid segment of the beta chain of LH/CG or to LHRH. Both Hecate-LH/CG and Phor14-LH/CG are remarkably effective in destroying human prostate and beast cancer xenografts in nude mice. LHRH-Hecate also destroys prostate cancers in nude mice. A major advantage of these compounds over currently used treatments is their ability to destroy metastatic cells in sites remote from the tumor. The only tissues other than the cancer cells affected are the testes and ovaries. These conjugates are not antigenic and can be administered repeatedly. The membrane-disrupting lytic peptides are up to 50 times more effective in killing cancer cells in vitro than normal cells. Other chemotherapeutic agents were equally potent in killing cancer and normal cells.