A long-trusted blood pressure medication could also show some effect to stop the growth of tumors, found a highly trained research team.
When scientists repurpose old drugs for new treatments, they can build on decades of safety data and manufacturing know-how—at times bringing promising therapies to patients faster, and at lower cost.
Now, a study published October 2025 in the peer-reviewed journal Scientific Advances reveals how hydralazine—a long-standing blood pressure medication—works at the molecular level, and also suggests that the same mechanism behind its cardiovascular benefits may also help slow the growth of glioblastoma, one of the most aggressive brain cancers.
Despite hydralazine’s 70-year history, first as a malaria drug and later as an anti-hypertensive medication, researchers say they’ve been puzzled by its “mechanism of action”—or exactly how it works.
Referring to hydralazine’s vessel-widening effect, Kyosuke Shishikura, PhD, a physician-scientist at the University of Pennsylvania and a co-author of the study, said via press release: “Hydralazine is one of the earliest vasodilators ever developed, and it’s still a first-line treatment for preeclampsia—a hypertensive disorder that accounts for 5% to 15% of maternal deaths worldwide.” Dr. Shishikura further explained, “It came from a ‘pre-target’ era of drug discovery, when researchers relied on what they saw in patients first and only later tried to explain the biology behind it.”
However, the Penn-led team of chemical biologists made an important discovery: that hydralazine blocks an enzyme called 2-aminoethanethiol dioxygenase (ADO), which normally acts as the body’s rapid-response oxygen sensor. This enzyme functions like an alarm—when oxygen drops, it sends signals that cause blood vessels to constrict.
Hydralazine binds directly to ADO and essentially silences this alarm. With ADO blocked, proteins known as RGS are no longer broken down, and their buildup tells blood vessels to stop tightening. That shift lowers calcium levels inside smooth muscle cells—the trigger for vascular relaxation—so blood pressure falls.
With this in mind, the researchers then made a surprising connection. Tumors such as glioblastoma often survive by adapting to extremely low-oxygen conditions, and ADO appears to support that survival strategy. Higher levels of ADO appeared to be linked to more aggressive disease.
When scientists tested hydralazine on brain cancer cells, they saw cells entering a dormant state known as “scenesence,” in which cancer growth and cell division stop. This suggests that targeting ADO may deprive tumors of a crucial coping mechanism.
The National Cancer Institute calls glioblastoma the most common form of brain cancer, accounting for up to 40% of all cancerous brain tumors in adults. An estimated 14,000 new U.S. cases are diagnosed each year.
Hydralazine is not without its risks and side effects, “including, for example, a lupus-like autoimmune syndrome, blood disorders, and nerve and liver toxicity,” the study states. Still, the findings open the door to designing new drugs that inhibit ADO more selectively, reach the brain more effectively, and improve treatments both for hypertensive disorders, such as preeclampsia, and life-threatening brain cancers.
Said Megan Matthews, PhD, an assistant chemistry professor at UPenn and a co-author of the study: “It’s rare that an old cardiovascular drug ends up teaching us something new about the brain. But that’s exactly what we’re hoping to find more of—unusual links that could spell new solutions.”
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