Targeted destruction of normal and cancer cells through lutropin/choriogonadotropin receptors using Hecate-betaCG conjugate.
A recent approach to cancer treatment is destruction of malignant and non-malignant tumors by hormonally targeted lytic peptides. The presence of lutropin/choriogonadotropin (LH/CG) receptors has been confirmed in several cancer cells (e.g. breast, ovarian, and prostate). In a series of experiments conducted in vitro, we have used a conjugate of the 23-amino acid lytic peptide Hecate and a 15-amino acid segment of beta-chain of CG. To test the hypothesis that Hecate-betaCG selectively destroys porcine granulosa and luteal cells, and Leydig cancer cell line (BLT-1) possessing LH/CG receptors, the conjugate was added to culture media at different concentrations of 0.5 to 10 micro M. Spleen cells and late passage of granulosa cancer cell line (KK-1) not-possessing LH/CG receptors were used as controls. The toxicity of Hecate-betaCG conjugate was concentration-dependent in all cell types but different among various cells. The toxicity of the conjugate to treated cells was closely correlated with the number of LH/CG receptors per cell. At low concentration (1 micro M), Hecate-betaCG was more cytotoxic to cells bearing LH/CG receptors than to controls (p < 0.01). In contrast to cells possessing LH/CG receptors, cancer cell line KK-1 and spleen cells were sensitive only at concentration of 5 micro M (p < 0.001). We conclude that Hecate-betaCG selectively kills cells expressing LH/CG receptors; its toxicity is dependent on the number of binding sites for LH/CG.
Zaleska
M
M
Institute of Animal Reproduction and Food Research Polish Academy of Sciences, Olsztyn, Poland.
Bodek
G
G
Jana
B
B
Hansel
W
W
Ziecik
A J
AJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D003338:Corpus Luteum / Q000166:cytology / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects; D007985:Leydig Cells / Q000187:drug effects; D008297:Male; D008555:Melitten / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009994:Osmolar Concentration; D020033:Protein Isoforms / Q000008:administration & dosage / Q000494:pharmacology; D011967:Receptors, Gonadotropin / Q000378:metabolism*; D011974:Receptors, LH / Q000187:drug effects*; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013552:Swine
D000970:Antineoplastic Agents; D006063:Chorionic Gonadotropin; D004338:Drug Combinations; D020033:Protein Isoforms; D011967:Receptors, Gonadotropin; D011974:Receptors, LH; C098827:hecate 1; D008555:Melitten