Human prostate cancer cells and xenografts are targeted and destroyed through luteinizing hormone releasing hormone receptors

Prostate. 2003 Sep 1;56(4):239-49. doi: 10.1002/pros.10259.

Abstract

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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight
  • Cell Death*
  • Culture Media
  • Gonadotropin-Releasing Hormone / chemistry
  • Gonadotropin-Releasing Hormone / pharmacology*
  • Humans
  • Male
  • Melitten / analogs & derivatives*
  • Melitten / pharmacology*
  • Mice
  • Mice, Nude
  • Necrosis
  • Neoplasms, Experimental
  • Peptides
  • Prostatic Neoplasms / pathology*
  • Receptors, LHRH / physiology*
  • Steroids / pharmacology
  • Transplantation, Heterologous
  • Tumor Cells, Cultured

Substances

  • Culture Media
  • Peptides
  • Receptors, LHRH
  • Steroids
  • hecate 1
  • Melitten
  • Gonadotropin-Releasing Hormone