Human prostate cancer cells and xenografts are targeted and destroyed through luteinizing hormone releasing hormone receptors.
BACKGROUND
A conjugate of a lytic peptide, hecate, and a 15-amino acid segment of the beta-chain of chorionic gonadotropin (CG) destroyed human prostate xenografts in nude mice by targeting LH receptors. Since these xenografts also express LHRH receptors, we prepared a LHRH-hecate conjugate and tested its ability to destroy PC-3 cells in vitro and in vivo.


METHODS
LHRH-hecate was added to cultures of PC-3, BRF 41 T, DU145, and LNCaP cells in the presence and absence of steroids. PC-3 xenografts were established in nude male mice, which were treated with LHRH-hecate.


RESULTS
Injections of LHRH-hecate resulted in tumor growth arrest and marked reduction of tumor burden (62.2 mg/g body weight in saline controls vs. 10.5 mg/g body weight in treated mice; P < 0.0001); unconjugated LHRH and hecate had no effect on tumor burden and tumor viability (48.5 mg/g body weight in LHRH treated animals vs. 63.2 mg/g body weight in hecate treated mice). Marked tumor necrosis occurred in conjugate treated mice. Removal of steroids from the culture media decreased the sensitivity of LNCaP and PC-3 cells to the LHRH-hecate; adding estrogen restored the sensitivity.


CONCLUSIONS
LHRH-hecate may be effective in treating hormone dependent and independent prostate cancers.
Leuschner
Carola
C
Pennington Biomedical Research Center, LSU, Baton Rouge, Louisiana 70808, USA. leuschc@pbrc.edu
Enright
Frederick M
FM
Gawronska-Kozak
Barbara
B
Hansel
William
W
D000818:Animals; D001835:Body Weight; D016923:Cell Death; D003470:Culture Media; D007987:Gonadotropin-Releasing Hormone / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008555:Melitten / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009336:Necrosis; D009374:Neoplasms, Experimental; D010455:Peptides; D011471:Prostatic Neoplasms / Q000473:pathology*; D011966:Receptors, LHRH / Q000502:physiology*; D013256:Steroids / Q000494:pharmacology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D003470:Culture Media; D010455:Peptides; D011966:Receptors, LHRH; D013256:Steroids; C098827:hecate 1; D008555:Melitten; D007987:Gonadotropin-Releasing Hormone