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.

Biomedicines
|August 27, 2021
PubMed

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.

Related Concept Videos

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
587
Combined Effects of Drugs: Synergism01:27

Combined Effects of Drugs: Synergism

Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
5.1K
Antihypertensive Drugs: Direct Renin Inhibitors01:25

Antihypertensive Drugs: Direct Renin Inhibitors

The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
936
Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists01:18

Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists

Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
251
Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors01:28

Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors

Phosphodiesterase 5 (PDE5) inhibitors are potent enzymes that function to hydrolyze cyclic nucleotides to their corresponding 5' monophosphates. Their unique biochemical properties have been applied in treating Pulmonary Arterial Hypertension (PAH).
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
282
Antihypertensive Drugs: Vasodilators01:23

Antihypertensive Drugs: Vasodilators

Vasodilators, primarily affecting the smooth muscles within arterial and venous walls, are commonly used for hypertension treatment. Medications such as minoxidil and hydralazine primarily target arteries and arterioles, while sodium nitroprusside acts on arterioles and venules. Minoxidil, functioning as a prodrug, is metabolized by hepatic sulfotransferase into its active form, minoxidil sulfate, after oral administration. This metabolite binds to the sulfonylurea receptor (SUR) component of...
1.6K