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Human prostate cancer cells and xenografts are targeted and destroyed through luteinizing hormone releasing hormone receptors
Author(s) -
Leuschner Carola,
Enright Frederick M.,
Gawronska–Kozak Barbara,
Hansel William
Publication year - 2003
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.10259
Subject(s) - endocrinology , medicine , du145 , lncap , human chorionic gonadotropin , luteinizing hormone , receptor , prostate cancer , hormone , biology , cancer
BACKGROUND A conjugate of a lytic peptide, hecate, and a 15‐amino acid segment of the β‐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. MATERIALS AND 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. Prostate 56: 239–249, 2003. © 2003 Wiley‐Liss, Inc.