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Updated: Mar 17, 2026

An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Anti-proliferative and pro-apoptotic effects of GHRH antagonists in prostate cancer
Laura Muñoz-Moreno1, Maria Isabel Arenas2, María J Carmena1
1Department of Systems Biology, Unit of Biochemistry and Molecular Biology, University of Alcalá, Alcalá de Henares, Spain.
Abstract:
Growth hormone-releasing hormone (GHRH) and its receptors have been implicated in the progression of various tumors. In vitro and in vivo studies have demonstrated that GHRH antagonists inhibit the growth of several cancers. GHRH antagonists, JMR-132 and JV-1-38 inhibit the growth of androgen-independent prostate tumors. Here we investigated the involvement of GHRH antagonists in proliferative and apoptotic processes. We used non-tumoral RWPE-1 and tumoral LNCaP and PC3 human prostatic epithelial cells, as well as an experimental model of human tumor PC3 cells. We evaluated the effects of JMR-132 and JV-1-38 antagonists on cell viability and proliferation in the three cell lines by means of MTT and BrdU assays, respectively, as well as on cell cycle and apoptotic process in PC3 cells. The expression levels of PCNA, p53, p21, CD44, Cyclin D1, c-myc, Bax and Bcl2 were determined in both in vivo and in vitro models by means of Western-blot and RT-PCR. GHRH antagonists suppressed cell proliferation and decreased the levels of the proliferation marker, PCNA, in the three cell lines and in PC3 tumor. GHRH antagonists led to an increase of cells in S-phase and a decrease in G1 and G2/M phases, and induced S-phase arrest and increase of apoptotic cells. The effects of GHRH-antagonists on cell cycle could be due to the changes observed in the expression of p21, p53, Bax, Bcl2, CD44, Cyclin D1, c-myc and caspase 3. Present results confirm and extend the role of GHRH antagonists as anti-proliferative and pro-apoptotic molecules in prostate cancer.
Insights
Growth hormone-releasing hormone (GHRH) antagonists inhibit prostate tumor growth by reducing proliferation and inducing apoptosis. These GHRH antagonists show promise as anti-cancer agents for prostate cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Endocrinology
Background:
- Growth hormone-releasing hormone (GHRH) and its receptors are linked to various tumor progressions.
- GHRH antagonists have demonstrated anti-cancer effects in preclinical studies.
- Specific GHRH antagonists, JMR-132 and JV-1-38, show potential against androgen-independent prostate tumors.
Purpose of the Study:
- To investigate the role of GHRH antagonists in the proliferative and apoptotic processes of prostate cancer cells.
- To evaluate the impact of JMR-132 and JV-1-38 on cell viability, proliferation, cell cycle, and apoptosis in human prostate cancer models.
Main Methods:
- Utilized non-tumoral (RWPE-1) and tumoral (LNCaP, PC3) human prostatic epithelial cell lines, plus an in vivo PC3 tumor model.
- Assessed cell viability (MTT) and proliferation (BrdU), cell cycle, and apoptosis.
- Quantified expression levels of key proteins (PCNA, p53, p21, CD44, Cyclin D1, c-myc, Bax, Bcl2, caspase 3) using Western blot and RT-PCR.
Main Results:
- GHRH antagonists significantly suppressed cell proliferation and decreased PCNA levels across all tested cell lines and in the PC3 tumor model.
- Antagonists induced S-phase arrest, increased the proportion of cells in S-phase, and reduced cells in G1 and G2/M phases.
- GHRH antagonists promoted apoptosis and altered the expression of cell cycle and apoptosis-related proteins (p53, p21, Bax, Bcl2, CD44, Cyclin D1, c-myc, caspase 3).
Conclusions:
- GHRH antagonists exhibit significant anti-proliferative effects on prostate cancer cells.
- These antagonists effectively induce apoptosis and modulate cell cycle progression in prostate cancer models.
- The findings support the role of GHRH antagonists as potent anti-proliferative and pro-apoptotic agents for prostate cancer therapy.
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