This Popular Medication Appears to Combat One of The Most Lethal Brain Tumors

Hydralazine has been prescribed for decades to manage high blood pressure, though its exact mechanism remained uncertain. A recent study has now clarified how the drug works and uncovered a surprising connection to aggressive brain cancers.

Researchers at the University of Pennsylvania examined hydralazines effects on both human and mouse cells. They discovered that the drug inhibits an enzyme known as 2-aminoethanethiol dioxygenase (ADO), which is also linked to the progression of glioblastoma, a severe form of brain cancer.

This new understanding of hydralazine could pave the way for innovative cancer therapies while enhancing its existing use for hypertension and preeclampsia.

"Hydralazine is among the first vasodilators ever created and remains a standard treatment for preeclampsia, a hypertensive condition responsible for a significant percentage of maternal deaths worldwide," explains Kyosuke Shishikura, a physician-scientist at the University of Pennsylvania. "It originated in an era when drugs were used based on observed effects in patients before researchers understood the underlying biology."

ADO is responsible for reactions that generate hypotaurine, a compound that encourages cancer cell growth. The enzyme acts as an "alarm bell," sensing low oxygen levels and initiating a response that narrows blood vessels by breaking down RGS proteins (regulators of G-protein signaling).

Previous studies have shown that glioblastoma tumors exploit high levels of ADO to produce hypotaurine, supporting cancer cell survival, proliferation, and stress tolerance. Until now, no inhibitors of ADO had been identified.

In the study, hydralazine was found to suppress ADO activity. This prevents the breakdown of RGS proteins, relaxes blood vessels, and lowers blood pressure. When applied to human glioblastoma cells, the drug effectively stopped tumor growth by blocking ADO.

While clinical trials in glioblastoma patients are still needed, these early results suggest a promising avenue for controlling the spread of this challenging cancer. Additionally, the findings clarify why hydralazine is effective against preeclampsia, offering opportunities to refine and personalize the drug to minimize side effects.

"Understanding hydralazine at a molecular level opens the door to safer, more targeted treatments for pregnancy-related hypertension, potentially improving outcomes for high-risk patients," says chemist Megan Matthews, also from the University of Pennsylvania.

The research indicates that more precise drugs can be developed for both high blood pressure and brain cancer, targeting specific cellular pathways while protecting healthy tissue. Because hydralazine is already widely used, this new knowledge provides scientists a head start in developing additional therapies based on the compound.

Future research may allow scientists to disable key defenses in glioblastoma cells, complementing existing treatments. "Its rare for a long-standing cardiovascular drug to reveal new insights about the brain," notes Matthews. "But discovering such unexpected connections could lead to breakthrough solutions."

The study has been published in Science Advances.

Hydralazine: A Dual-Action Drug with Unforeseen Potential

For decades, hydralazine has been a go-to medication for managing hypertension and preeclampsia. Its role in relaxing blood vessels and lowering blood pressure has been well-established. However, new research from the University of Pennsylvania has uncovered an unexpected connection between hydralazine and glioblastoma, an aggressive form of brain cancer.

Researchers have revealed that hydralazine works by inhibiting an enzyme called 2-aminoethanethiol dioxygenase (ADO), which plays a key role in the progression of glioblastoma. By blocking ADO, hydralazine prevents the breakdown of RGS proteins, ultimately halting tumor growth. This discovery could significantly impact both cancer therapies and the treatment of hypertensive conditions, including preeclampsia.

The implications of this study are vast. While hydralazine's primary use remains in managing hypertension and preeclampsia, its newfound connection to glioblastoma opens the door for innovative cancer treatments. Although clinical trials are still required, the drug's potential to slow the progression of brain cancer presents a promising new avenue for research.

Moreover, this insight into hydralazine's molecular mechanisms offers opportunities to refine the drug for more personalized and targeted treatments. Its established safety profile could be leveraged to develop more effective therapies with fewer side effects for both hypertensive and cancer patients.

In summary, hydralazine's dual action—addressing both cardiovascular conditions and potentially inhibiting brain cancer progression—marks a significant milestone in the evolution of this long-standing drug. Further studies could lead to breakthrough solutions in both the cardiovascular and oncology fields, with far-reaching impacts for patient care.

Sources:

• This Common Drug Seems to Fight One of The Deadliest Brain Cancers