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

Abstract

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.

• Authors: Laura Muñoz-Moreno, Andrew V Schally, Juan C Prieto, M José Carmena, Ana M Bajo
• Journal: The Prostate (Prostate) Vol. 78 Issue 12 Pg. 915-926 (09 2018) ISSN: 1097-0045 [Electronic] United States
• PMID: 29748961 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• GHRH(1-29)NH2, (PhAc-Ada)(0)-Tyr(1), Arg(2), Fpa(5,6), Ala(8), Har(9), Tyr(Me)(10), His(11), Orn(12,) Abu(15), His(20), Orn(21), Nle(27), Arg(28), Har(29)-
• Receptors, Neuropeptide
• Receptors, Pituitary Hormone-Regulating Hormone
• Vascular Endothelial Growth Factor A
• beta Catenin
• Sermorelin
• somatotropin releasing hormone receptor

Topics

• Apoptosis (drug effects)
• Cell Adhesion (drug effects)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Humans
• Male
• PC-3 Cells
• Prostatic Neoplasms (drug therapy, pathology)
• Receptors, Neuropeptide (antagonists & inhibitors)
• Receptors, Pituitary Hormone-Regulating Hormone (antagonists & inhibitors)
• Resting Phase, Cell Cycle
• Sermorelin (analogs & derivatives, pharmacology)
• Vascular Endothelial Growth Factor A (analysis, metabolism)
• Wound Healing (drug effects)
• beta Catenin (analysis)