Targeted destruction of androgen-sensitive and -insensitive prostate cancer cells and xenografts through luteinizing hormone receptors.
BACKGROUND
We have prepared a conjugate of a lytic peptide (hecate) and a 15-amino acid segment of the beta-chain of LH to test the concept that this conjugate will target cancer cells expressing LH receptors.


METHODS
Hecate-betaLH was added in vitro to cultures of Chinese hamster ovary (CHO) cells with and without LH receptors and to prostate cancer cells in the presence or absence of steroids, follicle-stimulating hormone (FSH), epidermal growth factor (EGF), or betaLH. PC-3 xenografts were established in male athymic nude mice and treated once a week for 3 weeks with hecate-betaLH via the lateral tail vein.


RESULTS
The conjugate showed concentration-dependent toxicity for the following prostate cancer cell lines: BRF 41 T>DU145>PC-3>LNCaP, according to their LH receptor capacities. Steroid removal reduced sensitivity to the drug in a reversible manner. Hecate-betaLH reduced the tumor burden in the nude mice from 60 to 12.5 mg/g body weight.


CONCLUSIONS
We conclude that the hecate-betaLH conjugate selectively kills androgen-dependent and-independent prostate cancer cells both in vivo and in vitro; its toxicity depends on the number of LH receptor sites present.
Leuschner
C
C
Pennington Biomedical Research Center, Reproductive Biology, LSU, 6400 Perkins Road, Baton Rouge, LA 70808-4124, USA. leuschc@mhs.prbc.edu
Enright
F M
FM
Melrose
P A
PA
Hansel
W
W
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells / Q000187:drug effects / Q000378:metabolism; D002606:Charcoal / Q000494:pharmacology; D006224:Cricetinae; D004337:Drug Carriers; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006801:Humans; D007986:Luteinizing Hormone / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D008555:Melitten / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009376:Neoplasms, Hormone-Dependent; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D011974:Receptors, LH / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D004337:Drug Carriers; D010446:Peptide Fragments; D011974:Receptors, LH; C098827:hecate 1; D002606:Charcoal; D008555:Melitten; D004815:Epidermal Growth Factor; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone