title: LHRH-conjugated lytic peptides directly target prostate cancer cells.
abstract: 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 IC(50) concentrations for LNCaP cells, 4.4 and 9.1μM; for DU-145 cells, 4.8 and 5.7μM; and for PC-3 cells, 4.4 and 8.2μM, 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 3h of exposure to either peptide; after 6h, there were significant reductions in cell numbers. Exposure of PC-3 cells for 24h 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.
authors.affiliation: Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL 36088, USA. cyates@tuskegee.edu
authors.forename: Clayton
authors.initials: C
authors.lastname: Yates
authors.forename: Starlette
authors.initials: S
authors.lastname: Sharp
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Jones
authors.forename: Daphne
authors.initials: D
authors.lastname: Topps
authors.forename: Mathew
authors.initials: M
authors.lastname: Coleman
authors.forename: Ritu
authors.initials: R
authors.lastname: Aneja
authors.forename: Jesse
authors.initials: J
authors.lastname: Jaynes
authors.forename: Timothy
authors.initials: T
authors.lastname: Turner
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004847:Epithelial Cells / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011467:Prostate / Q000166:cytology; D011471:Prostatic Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D010446:Peptide Fragments; D007987:Gonadotropin-Releasing Hormone