In series of experiments conducted in vitro, we have established the concept that conjugates of the lytic
peptides Hecate or Phor14 with a fragment of the beta chain of LH (
amino acids 80-94) selectively destroy both
androgen sensitive and insensitive human
prostate cancer cells. Extraction of
steroids from the culture medium by
charcoal reduced the ability of the conjugates to kill LNCaP, BRF41T and PC-3 cells. Addition of
hormones known to up-regulate
LH receptors (
estradiol,
testosterone or FSH) to the culture medium restored the ability of the conjugates to kill these cell lines. The toxicity of the conjugates (EC(50)) to these cell lines was closely correlated to their LH binding capacities (f mol/10(6) cells). In series of in vivo experiments we have shown that both the Hecate and
Phor14-betaLH conjugates are remarkably effective in causing
tumor cell
necrosis and cessation of
tumor growth in nude athymic mice. Treatment with
Hecate-betaLH (12 mg/kg
body weight) resulted in a reduction of
tumor burden (mg
tumor/g
body weight) from 60 to 14 (P<0.0001); treatment with
Phor14-betaLH (12 mg/kg
body weight) reduced
tumor burden to 27 mg (P<0.0001). Treatment with a high dose of
Phor14-betaLH (24 mg/kg
body weight) reduced the
tumor burden from 60 to 12 mg/kg P<0.0001). Pretreatment of animals receiving a low dose of Phor14-betaLH (12 mg/kg) with either
estradiol or
follicle stimulating hormone, (FSH) resulted in reduction of
tumor burden from 60 to 11 mg/kg. Administration of a second 3-week treatment after a one month recovery period caused complete regression of more than 75 percent of the
tumors. No changes in
body weight or histological abnormalities were found in any of the organs examined, except the testes.