LHRH-conjugated lytic peptides directly target prostate cancer cells

Prostate cancer is the second leading cause of cancer deaths among men. For patients with hormone-refractory disease, few treatments are available once the tumor has metastasized beyond the prostate. In the present study, two conjugated lytic peptide sequences (named JCHLHRH and JC21LHRH) were designed to target luteinizing hormone–releasing hormone receptors (LHRH-R). Our results indicate that human prostate cancer cell lines were sensitive to both LHRH-conjugated and non-conjugated lytic peptides, with IC50 concentrations for LNCaP cells, 4.4 and 9.1 μM; for DU-145 cells, 4.8 and 5.7 μM; and for PC-3 cells, 4.4 and 8.2 μM, respectively. JCHLHRH and JC21LHRH were nontoxic to normal primary human prostate epithelial cells or to bone marrow stromal cells in co-culture. There were morphological changes in PC-3 cells after 3 h of exposure to either peptide; after 6 h, there were significant reductions in cell numbers. Exposure of PC-3 cells for 24 h to either JCHLHRH or JC21LHRH blocked their growth over 3 days. Since JCHLHRH and JC21LHRH have specificity for and anti-proliferative activity against tumor cells, and low toxicity for normal prostate cells, these peptides could serve as a new type of therapy for prostate cancer.

Graphical abstractNovel LHRH–lytic conjugated peptides inhibit prostate cancer proliferation.Figure optionsDownload full-size imageDownload as PowerPoint slide