Format

Send to

Choose Destination
Endocr Relat Cancer. 2018 Oct 1. pii: ERC-18-0454.R1. doi: 10.1530/ERC-18-0454. [Epub ahead of print]

Anti-cancer effect of GV1001 for prostate cancer; function as a ligand of GnRHR.

Author information

1
J Kim, Department of Pharmacy, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, SEOUL, Korea (the Republic of).
2
D Yadav, Department of Pharmacy, Gachon Institute of Pharmaceutical Science and College of Pharmacy, Gachon University, Incheon, Korea (the Republic of).
3
S Kim, Department of Pharmacy, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, SEOUL, Korea (the Republic of).
4
M Lee, Department of Pharmacy, College of Pharmacy, Dongguk University, Goyang, Korea (the Republic of).
5
J Park, Department of Pharmacy, College of Pharmacy, Dongguk University, Goyang, Korea (the Republic of).
6
B Kim, Department of Veterinary Science, College of Veterinary Medicine, Chonbuk National University, Iksan, Korea (the Republic of).
7
M Kim, Department of Pharmacy, Gachon Institute of Pharmaceutical Science and College of Pharmacy, Gachon University , Incheon, Korea (the Republic of).
8
H Park, Department of Pharmacy, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, SEOUL, Korea (the Republic of).
9
K Kang, Department of Pharmacy, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, SEOUL, Korea (the Republic of).

Abstract

GV1001, a 16-amino acid fragment of the human telomerase reverse transcriptase catalytic subunit (hTERT), has been developed as an injectable formulation of cancer vaccine. Here, we revealed for the first time that GV1001 is a novel ligand for gonadotropin-releasing hormone receptor (GnRHR). The docking prediction for GV1001 against GnRHR showed high binding affinity. Binding of GV1001 to GnRHR stimulated the Gαs-coupled cAMP signaling pathway and antagonized Gαq-coupled Ca2+ release by leuprolide acetate (LA), a GnRHR agonist. Repeated injection of GV1001 attenuated both serum testosterone level and seminal vesicle weight via desensitization of hypothalamic-pituitary-gonadal (HPG) axis. We then tested whether GV1001 has an inhibitory effect on tumor growth of LNCaP cells, androgen receptor-positive human prostate cancer (PCa) cells. GV1001 significantly inhibited tumor growth and induced apoptosis in LNCaP-implanted xenografts. Interestingly, mRNA expressions of matrix metalloproteinase2 and matrix metalloproteinase9 were suppressed by GV1001, but not by LA. Moreover, GV1001 significantly inhibited the proliferation and migration of PCa cells and induced apoptosis in a concentration-dependent manner. Our findings suggest that GV1001 functions as a biased GnRHR ligand to selectively stimulate the Gαs/cAMP pathway, with anti-proliferative and anti-migratory effects on human PCa.

PMID:
30400054
DOI:
10.1530/ERC-18-0454

Supplemental Content

Full text links

Icon for Sheridan PubFactory
Loading ...
Support Center