NDLI: In Search of the Molecular Mechanisms Mediating the Inhibitory Effect of the GnRH Antagonist Degarelix on Human Prostate Cell Growth

Content Provider	PubMed Central
Author	Sakai, Monica Martinez-arguelles, Daniel B. Patterson, Nathan H. Chaurand, Pierre Papadopoulos, Vassilios
Editor	Kyprianou, Natasha
Copyright Year	2015
Abstract	Degarelix is a gonadrotropin-releasing hormone (GnRH) receptor (GnRHR) antagonist used in patients with prostate cancer who need androgen deprivation therapy. GnRHRs have been found in extra-pituitary tissues, including prostate, which may be affected by the GnRH and GnRH analogues used in therapy. The direct effect of degarelix on human prostate cell growth was evaluated. Normal prostate myofibroblast WPMY-1 and epithelial WPE1-NA22 cells, benign prostatic hyperplasia (BPH)-1 cells, androgen-independent PC-3 and androgen-dependent LNCaP prostate cancer cells, as well as VCaP cells derived from a patient with castration-resistant prostate cancer were used. Discriminatory protein and lipid fingerprints of normal, hyperplastic, and cancer cells were generated by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS). The investigated cell lines express GNRHR1 and GNRHR2 and their endogenous ligands. Degarelix treatment reduced cell viability in all prostate cell lines tested, with the exception of the PC-3 cells; this can be attributed to increased apoptosis, as indicated by increased caspase 3/7, 8 and 9 levels. WPE1-NA22, BPH-1, LNCaP, and VCaP cell viability was not affected by treatment with the GnRH agonists leuprolide and goserelin. Using MALDI MS, we detected changes in m/z signals that were robust enough to create a complete discriminatory profile induced by degarelix. Transcriptomic analysis of BPH-1 cells provided a global map of genes affected by degarelix and indicated that the biological processes affected were related to cell growth, G-coupled receptors, the mitogen-activated protein kinase (MAPK) pathway, angiogenesis and cell adhesion. Taken together, these data demonstrate that (i) the GnRH antagonist degarelix exerts a direct effect on prostate cell growth through apoptosis; (ii) MALDI MS analysis provided a basis to fingerprint degarelix-treated prostate cells; and (iii) the clusters of genes affected by degarelix suggest that this compound, in addition to its known use in the treatment of prostate cancer, may be efficacious in BPH.
Related Links	http://dx.doi.org/10.1371/journal.pone.0120670
Starting Page	120670
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	3
Volume Number	10
Language	English
Publisher	Public Library of Science
Publisher Date	2015-03-26
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Treatment with a GnRH receptor agonist, but not the GnRH receptor antagonist degarelix, induces atherosclerotic plaque instability in ApoE −/− mice

Neo/adjuvant ADT to EBRT: Randomized phase 2 trial of the oral GnRH antagonist, TAK-385 (relugolix, RGX) and degarelix (DGX) in patients (pts) with prostate cancer (PC)

PSA-PFS in metastatic or high risk prostate cancer patients treated with GnRH antagonist (degarelix) versus LHRH agonists – A pooled analysis of data from the Americas, Europe and Asia

The Efficacy and Safety of Degarelix, a GnRH Antagonist: A 12-month, Multicentre, Randomized, Maintenance Dose-finding Phase II Study in Japanese Patients with Prostate Cancer

Degarelix, a novel GnRH antagonist, causes minimal histamine release compared with cetrorelix, abarelix and ganirelix in an ex vivo model of human skin samples

Pharmacokinetic/Pharmacodynamic Modellingof GnRH Antagonist Degarelix: A Comparisonof the Non-linear Mixed-Effects Programs NONMEM and NLME

The inhibitory effect of melatonin on human prostate cancer

Inhibitory Effect of Zinc on Human Prostatic Carcinoma Cell Growth

Genetic mechanisms mediating kisspeptin regulation of GnRH gene expression

In Search of the Molecular Mechanisms Mediating the Inhibitory Effect of the GnRH Antagonist Degarelix on Human Prostate Cell Growth

Similar Documents

Treatment with a GnRH receptor agonist, but not the GnRH receptor antagonist degarelix, induces atherosclerotic plaque instability in ApoE −/− mice

Neo/adjuvant ADT to EBRT: Randomized phase 2 trial of the oral GnRH antagonist, TAK-385 (relugolix, RGX) and degarelix (DGX) in patients (pts) with prostate cancer (PC)

PSA-PFS in metastatic or high risk prostate cancer patients treated with GnRH antagonist (degarelix) versus LHRH agonists – A pooled analysis of data from the Americas, Europe and Asia

The Efficacy and Safety of Degarelix, a GnRH Antagonist: A 12-month, Multicentre, Randomized, Maintenance Dose-finding Phase II Study in Japanese Patients with Prostate Cancer

Degarelix, a novel GnRH antagonist, causes minimal histamine release compared with cetrorelix, abarelix and ganirelix in an ex vivo model of human skin samples

Pharmacokinetic/Pharmacodynamic Modellingof GnRH Antagonist Degarelix: A Comparisonof the Non-linear Mixed-Effects Programs NONMEM and NLME

The inhibitory effect of melatonin on human prostate cancer

Inhibitory Effect of Zinc on Human Prostatic Carcinoma Cell Growth

Genetic mechanisms mediating kisspeptin regulation of GnRH gene expression

In Search of the Molecular Mechanisms Mediating the Inhibitory Effect of the GnRH Antagonist Degarelix on Human Prostate Cell Growth