title: The cyclic pentapeptide d-Arg3FC131, a CXCR4 antagonist, induces apoptosis of somatotrope tumor and inhibits tumor growth in nude mice.
abstract: The interaction between the chemokine stromal cell-derived factor 1 and its receptor CXCR4 plays an important role in GH production and cell proliferation in normal and tumorous pituitary somatotrope cells. Therefore, the chemokine receptor CXCR4 could be an attractive target for antitumor drugs in patients with acromegaly. A synthetic antagonist of CXCR4, cyclic pentapeptide d-Arg3FC131 (c[Gly1-d-Tyr2-d-Arg3-Arg4-Nal5]) significantly inhibited GH production and proliferation of GH3 somatotrope tumor cells in vitro. It also induced apoptosis of GH3 cells through activation of the caspase-3 pathway. Systemic administration of d-Arg3FC131 inhibited the growth of GH3 cell xenografts in immunodeficient nude mice by inducing apoptosis and suppressing the proliferation of tumor cells. These results indicate that d-Arg3FC131 might have potential for the treatment of pituitary tumors producing excess GH in patients with acromegaly.
authors.affiliation: Severance Hospital Integrative Research Institute for Cerebral & Cardiovascular Diseases and Department of Internal Medicine, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Jeong Mo
authors.initials: JM
authors.lastname: Kim
authors.forename: Yong-Ho
authors.initials: YH
authors.lastname: Lee
authors.forename: Cheol Ryong
authors.initials: CR
authors.lastname: Ku
authors.forename: Eun Jig
authors.initials: EJ
authors.lastname: Lee
mesh_terms: D000256:Adenoviridae; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000235:genetics; D013006:Growth Hormone / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009842:Oligopeptides / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology* / Q000627:therapeutic use; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D052683:Somatotrophs / Q000187:drug effects* / Q000473:pathology*
chemical_list: C486264:Cxcr4 protein, rat; D009842:Oligopeptides; D010456:Peptides, Cyclic; D019718:Receptors, CXCR4; D013006:Growth Hormone