Growth hormone‐releasing hormone receptor antagonists modify molecular machinery in the progression of prostate cancer

• Published in: The Prostate 2018-09, Vol.78 (12), p.915-926
• Main Authors: Muñoz‐Moreno, Laura, Schally, Andrew V., Prieto, Juan C., Carmena, M. José, Bajo, Ana M.
• Format: Article
• Language: English
• Subjects: Angiogenesis; antagonists; Apoptosis; Apoptosis - drug effects; beta Catenin - analysis; Cell adhesion; Cell adhesion & migration; Cell Adhesion - drug effects; Cell Cycle - drug effects; Cell Line, Tumor; Cell migration; Cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; E-cadherin; Gelatinase A; Gelatinase B; GHRH‐R; Growth hormone-releasing hormone; Growth hormones; Humans; Male; Malignancy; p53 Protein; PC-3 Cells; Phenotypes; Proliferating cell nuclear antigen; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Receptors, Neuropeptide - antagonists & inhibitors; Receptors, Pituitary Hormone-Regulating Hormone - antagonists & inhibitors; Resting Phase, Cell Cycle; Sermorelin - analogs & derivatives; Sermorelin - pharmacology; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - analysis; Vascular Endothelial Growth Factor A - metabolism; Wound Healing - drug effects
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.23648

Background Therapeutic strategies should be designed to transform aggressive prostate cancer phenotypes to a chronic situation. To evaluate the effects of the new growth hormone‐releasing hormone receptor (GHRH‐R) antagonists: MIA‐602, MIA‐606, and MIA‐690 on processes associated with cancer progression as cell proliferation, adhesion, migration, and angiogenesis. Methods We used three human prostate cell lines (RWPE‐1, LNCaP, and PC3). We analyzed several molecules such as E‐cadherin, β‐catenin, Bcl2, Bax, p53, MMP2, MMP9, PCNA, and VEGF and signaling mechanisms that are involved on effects exerted by GHRH‐R antagonists. Results GHRH‐R antagonists decreased cell viability and provoked a reduction in proliferation in LNCaP and PC3 cells. Moreover, GHRH‐R antagonists caused a time‐dependent increase of cell adhesion in all three cell lines and retarded the wound closure with the highest value with MIA‐690 in PC3 cells. GHRH‐R antagonists also provoked a large number of cells in SubG0 phase revealing an increase in apoptotic cells in PC3 cell line. Conclusions Taken all together, GHRH‐R antagonists of the MIAMI series appear to be inhibitors of tumor progression in prostate cancer and should be considered for use in future therapeutic strategies on this malignancy.