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Updated: Oct 22, 2025

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Hydralazine and Enzalutamide: Synergistic Partners against Prostate Cancer
Nair Lopes1, Mariana Brütt Pacheco1, Diana Soares-Fernandes1
1Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.
Abstract:
Advanced prostate cancers frequently develop resistance to androgen-deprivation therapy with serious implications for patient survival. Considering their importance in this type of neoplasia, epigenetic modifications have drawn attention as alternative treatment strategies. The aim of this study was to assess the antitumoral effects of the combination of hydralazine, a DNA methylation inhibitor, with enzalutamide, an antagonist of the androgen receptor, in prostate cancer cell lines. Several biological parameters, such as cell viability, proliferation, DNA damage, and apoptosis, as well as clonogenic and invasive potential, were evaluated. The individual treatments with hydralazine and enzalutamide exerted growth-inhibitory effects in prostate cancer cells and their combined treatment displayed synergistic effects. The combination of these two drugs was very effective in decreasing malignant features of prostate cancer and may become an alternative therapeutic option for prostate cancer patient management.
Insights
Combining hydralazine (a DNA methylation inhibitor) with enzalutamide (an androgen receptor antagonist) shows synergistic effects against advanced prostate cancer. This combination effectively reduces cancer cell viability and invasiveness, offering a potential new therapeutic strategy.
Area of Science:
- Oncology
- Epigenetics
- Pharmacology
Background:
- Advanced prostate cancer often develops resistance to androgen-deprivation therapy (ADT).
- Epigenetic modifications are crucial in cancer development and present potential therapeutic targets.
- ADT resistance significantly impacts patient survival rates in advanced prostate cancer.
Purpose of the Study:
- To evaluate the combined antitumoral effects of hydralazine and enzalutamide in prostate cancer cell lines.
- To investigate the impact of epigenetic modification combined with androgen receptor antagonism on cancer progression.
- To explore novel therapeutic strategies for overcoming ADT resistance in prostate cancer.
Main Methods:
- Prostate cancer cell lines were treated with hydralazine (DNA methylation inhibitor) and enzalutamide (androgen receptor antagonist) individually and in combination.
- Assessed were key biological parameters including cell viability, proliferation, DNA damage, and apoptosis.
- Evaluated were the effects on clonogenic and invasive potential of cancer cells.
Main Results:
- Both hydralazine and enzalutamide demonstrated individual growth-inhibitory effects on prostate cancer cells.
- The combination treatment exhibited synergistic antitumoral activity, surpassing the effects of individual drugs.
- Combined therapy significantly reduced malignant features, including proliferation and invasiveness.
Conclusions:
- The combination of hydralazine and enzalutamide demonstrates potent synergistic antitumoral effects in prostate cancer.
- This combination therapy effectively diminishes key malignant characteristics of prostate cancer cells.
- This drug combination represents a promising alternative therapeutic option for managing advanced prostate cancer, potentially overcoming resistance mechanisms.
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