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 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.
Yates
Clayton
C
Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL 36088, USA. cyates@tuskegee.edu
Sharp
Starlette
S
Jones
Jacqueline
J
Topps
Daphne
D
Coleman
Mathew
M
Aneja
Ritu
R
Jaynes
Jesse
J
Turner
Timothy
T
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*
D000970:Antineoplastic Agents; D010446:Peptide Fragments; D007987:Gonadotropin-Releasing Hormone