Destruction of breast cancers and their metastases by lytic peptide conjugates in vitro and in vivo.
In a series of in vivo and in vitro experiments, the concept has been established that breast cancer cells that express LH/CG or LHRH receptors can be targeted and destroyed by constructs consisting of a lytic peptide moiety and a 15-amino acid segment of the beta-chain of CG or by an LHRH lytic peptide conjugate. Data obtained in vitro established the validity of this concept, showed the specificities of the Hecate-betaCG, and Phor14 and Phor21-betaCG conjugates in killing cells that express functional LH/CG receptors and proved that the LH/CG receptor capacity is directly related to the compound's specificity. In in vivo experiments, Hecate-betaCG, Phor14-betaCG, and Phor21-betaCG(ala) each caused highly significant reductions of tumor volume and tumor burden in nude mice bearing breast cancer xenografts; Hecate and Phor21 alone or conjugated with non-specific peptides were not effective. Most importantly, the lytic peptide conjugates were all highly effective in targeting and destroying disseminated breast cancer metastases in lymph nodes, bones, lungs and other organs.
Hansel
William
W
Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA 70808, United States. hanselw@pbrc.edu
Enright
Fred
F
Leuschner
Carola
C
D000595:Amino Acid Sequence; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy*; D016923:Cell Death; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000737:chemistry / Q000627:therapeutic use*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000627:therapeutic use*; D008156:Luciferases / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008555:Melitten / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010446:Peptide Fragments / Q000737:chemistry / Q000627:therapeutic use*; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use*; D013116:Spinal Cord / Q000473:pathology; D047368:Tumor Burden
D018997:Chorionic Gonadotropin, beta Subunit, Human; D010446:Peptide Fragments; D010455:Peptides; C532487:Phor14-betaCG(ala) protein; C480619:hecate-chorionic gonadotropin beta-subunit conjugate; D008555:Melitten; D007987:Gonadotropin-Releasing Hormone; D008156:Luciferases