Anti-neoplastic properties of hydralazine in prostate cancer

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Prostate cancer (PCa) poses a significant global health burden, with limited effective treatments for advanced stages.
• Aberrant DNA methylation leading to gene silencing is a hallmark of PCa, making DNA methylation inhibitors a promising therapeutic avenue.

Purpose of the Study:

• To investigate the anti-cancer properties of hydralazine, a DNA methyltransferases (DNMT) inhibitor, in prostate cancer cell lines.
• To elucidate the molecular mechanisms underlying hydralazine's effects on PCa cells.

Main Methods:

• In vitro assays were performed on PCa cell lines treated with hydralazine.
• Assessed were cell growth, apoptosis, invasiveness, cell cycle, DNA damage, DNMT expression, promoter methylation, and gene re-expression.
• Protein array analysis was used to identify signaling pathways affected by hydralazine.

Main Results:

• Hydralazine demonstrated dose- and time-dependent inhibition of PCa cell growth, increased apoptosis, and reduced invasiveness.
• The drug induced cell cycle arrest and DNA damage, particularly in DU145 cells.
• Hydralazine decreased DNMT1, DNMT3a, and DNMT3b mRNA and DNMT1 protein levels, reduced promoter methylation of GSTP1, BCL2, and CCND2, and restored their transcript expression.
• Androgen receptor expression and its target p21 were restored in DU145 cells, with evidence suggesting EGF receptor signaling pathway blockage.

Conclusions:

• Hydralazine exhibits significant anti-cancer properties against prostate cancer cells in vitro.
• It effectively targets aberrant DNA methylation and restores tumor suppressor gene expression.
• Hydralazine represents a potential therapeutic agent for advanced prostate cancer, possibly through mechanisms involving EGF receptor signaling inhibition.