Targeted Destruction of Normal and Cancer Cells Through Lutropin/Choriogonadotropin Receptors Using Hecate-βCG Conjugate

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Abstract
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 β-chain of CG. To test the hypothesis that Hecate-βCG 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 µM. 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-βCG 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 µM), Hecate-βCG 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 µM (p < 0.001). We conclude that Hecate-βCG selectively kills cells expressing LH/CG receptors; its toxicity is dependent on the number of binding sites for LH/CG.

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