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ORIGINAL RESEARCH ARTICLE

Targeted Ablation of Prostate Carcinoma Cells Through LH Receptor Using Hecate-CGß Conjugate: Functional Characteristic and Molecular Mechanism of Cell Death Pathway

Gabriel Bodek^*,1, Anna Kowalczyk^*, Agnieszka Waclawik^*, Ilpo Huhtaniemi^, and Adam J. Ziecik^*

^* Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-714 Olsztyn, Poland; Department of Physiology, University of Turku, Finland; and Institute of Reproductive and Developmental Biology, Imperial College London, London W12 ONN, United Kingdom

To whom requests for reprints should be addressed at ¹ Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-714 Olsztyn, Poland. E-mail: gbodek{at}pan.olsztyn.pl

A Hecate-CGß conjugate (lytic peptide and ß-chorionic gonadotropin) selectively destroyed cells possessing LH receptors. This study described functional characteristics of the conjugate and the molecular mechanism of the cell death pathway in prostate cancer cells. Based on in vitro studies, we conclude that the conjugate kills cells possessing luteinizing hormone receptors (LHR) faster than Hecate alone. Competitive studies have shown that blocking of LHR by preincubation with chorionic gonadotropin (100 ng/ml) reduced toxicity of the conjugate in low concentrations. Further studies have also shown that the conjugate in treated cells both did not induce internucleosomal DNA fragmentation and did not induce morphological changes in cells characterized as having apoptotic features. These results proved that cells died by necrosis rather than apoptosis after the conjugate treatment.

Key Words: lytic peptide • prostate cancer • Hecate-CGß conjugate

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