A common, decades-old blood pressure medication is showing surprising promise in the fight against an aggressive brain cancer, glioblastoma, according too research published today in Science Advances. the University of Pennsylvania study not only reveals hydralazine‘s previously unknown mechanism of action – after nearly 70 years of use – but also demonstrates its ability to halt tumor growth by inducing cellular “hibernation” rather than outright destruction. This discovery could offer a new therapeutic avenue for glioblastoma, a cancer with a especially grim prognosis and limited treatment options, impacting an estimated 14,000 Americans each year.
A decades-old blood pressure medication, hydralazine, has been found to halt the growth of an aggressive form of brain cancer, according to a new study from the University of Pennsylvania. The discovery, published in Science Advances, also reveals the drug’s long-elusive mechanism of action after nearly 70 years in medical use.
Hydralazine is commonly used to treat pre-eclampsia, a dangerous pregnancy complication characterized by high blood pressure and organ damage, affecting 5 to 15% of maternal deaths globally. Despite its widespread use since the 1950s, how the drug actually worked at a molecular level remained a mystery. Understanding the underlying mechanisms of pre-eclampsia and effective treatments is a critical area of public health research.
“Hydralazine was developed in a ‘pre-molecular target’ era,” explained Dr. Keisuke Shishikura, a researcher and physician at the University of Pennsylvania. “Drugs were adopted based on their clinical effects before we understood how they worked at the cellular level.”
The research team discovered that hydralazine inhibits an oxygen-sensitive enzyme called 2-aminoethanethiol dioxygenase (ADO). This enzyme acts as a key regulator, signaling blood vessels when to constrict. When ADO is blocked, proteins that regulate vascular constriction accumulate, effectively telling blood vessels to relax and lowering blood pressure.
Surprisingly, researchers found that the same biological pathway controlling blood vessel constriction also plays a crucial role in the survival of glioblastoma cells – one of the most lethal and aggressive types of brain cancer. Glioblastoma tumors are known for their ability to thrive in low-oxygen environments.
Collaborating with researchers at the University of Texas and the University of Florida, the team used X-ray crystallography to confirm that hydralazine directly binds to the iron center within the ADO enzyme. They then tested the drug’s effects on glioblastoma cells.
The study found that hydralazine doesn’t directly kill cancer cells, but instead pushes them into a state of cellular senescence – a form of “hibernation” where cells stop dividing without causing inflammation or increasing resistance to traditional treatments. This effectively halts tumor growth. The findings suggest a potential new approach to cancer treatment focused on slowing, rather than immediately destroying, tumor cells.
“Understanding this mechanism opens the door to developing safer and more effective treatments for both pregnancy disorders and brain tumors,” said study co-author Meghan Matthews. She also noted that pre-eclampsia disproportionately affects Black women in the United States, making the discovery of more targeted treatment options particularly important.
The researchers are now working to design new ADO inhibitors that are more precise and can effectively cross the blood-brain barrier to directly reach tumor tissues.
This research highlights the potential of revisiting older drugs, researchers say, as they may hold unexpected therapeutic promise in complex health areas. The study underscores the value of continued investigation into established medications to uncover new applications and improve patient outcomes.
