Conjugates of lytic peptides and LHRH or betaCG target and cause necrosis of prostate cancers and metastases.
In a series of in vivo and in vitro experiments, it was shown that membrane disrupting lytic peptides (Hecate, Phor14, or Phor21) conjugated to a 15 amino acid segment of the beta chain of CG or to LHRH were able to target and destroy hormone dependent and independent human prostate cancer xenografts in nude mice. In vitro sensitivity of the cells to the drugs was directly related to LH/CG receptor expression, and pretreatment in vitro or in vivo with estrogens or FSH to enhance LH/CG receptor expression capacity and increased sensitivity to the drugs. Administration of unconjugated Hecate and LHRH was ineffective. Most importantly, all of the lytic peptide-betaCG conjugates tested were highly effective in destroying prostate cancer metastatic cells in lymph nodes, bones and lungs.
Hansel
William
W
Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA 70808, United States. hanselw@pbrc.edu
Leuschner
Carola
C
Enright
Fred
F
D000818:Animals; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000494:pharmacology / Q000627:therapeutic use; D007987:Gonadotropin-Releasing Hormone / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008555:Melitten / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D009336:Necrosis / Q000139:chemically induced; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology
D018997:Chorionic Gonadotropin, beta Subunit, Human; C480619:hecate-chorionic gonadotropin beta-subunit conjugate; D008555:Melitten; D007987:Gonadotropin-Releasing Hormone