Targeted ablation of prostate carcinoma cells through LH receptor using Hecate-CGbeta conjugate: functional characteristic and molecular mechanism of cell death pathway.
A Hecate-CGbeta conjugate (lytic peptide and beta-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.
Bodek
Gabriel
G
Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-714 Olsztyn, Poland. gbodek@pan.olsztyn.pl
Kowalczyk
Anna
A
Waclawik
Agnieszka
A
Huhtaniemi
Ilpo
I
Ziecik
Adam J
AJ
D000818:Animals; D045744:Cell Line, Tumor / Q000187:drug effects* / Q000473:pathology; D002462:Cell Membrane / Q000187:drug effects / Q000473:pathology; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis; D008297:Male; D008555:Melitten / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D009336:Necrosis; D011471:Prostatic Neoplasms; D012333:RNA, Messenger / Q000096:biosynthesis; D011974:Receptors, LH / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D006063:Chorionic Gonadotropin; D018997:Chorionic Gonadotropin, beta Subunit, Human; D012333:RNA, Messenger; D011974:Receptors, LH; C098827:hecate 1; C480619:hecate-chorionic gonadotropin beta-subunit conjugate; D008555:Melitten; D007770:L-Lactate Dehydrogenase