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.

Oncotarget
|July 25, 2016
PubMed

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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