A group of Penn researchers found that a common blood pressure medicine can be used to prevent brain cancer cells from growing.
After trying to understand how the drug, hydralazine, works at a molecular level, the researchers discovered that it blocks a certain oxygen-sensing enzyme. They later discovered that the same enzyme can be used to prevent brain cancer cells from growing.
Typically sold under the brand name “Apresoline,” hydralazine is used to treat high blood pressure and control hypertension during emergency situations or pregnancy, according to the Mayo Clinic.
“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 5-15% of maternal deaths worldwide,” Penn physician-scientist Kyosuke Shishikura said to Penn Today.
Specifically, the drug’s effectiveness comes from hydralazine’s ability to bind to the oxygen-sensing enzyme, which mutes a signal that constricts blood vessels. Shishikura collaborated with structural biochemists at the University of Texas and neuroscientists at the University of Florida using X-ray crystallography to determine if hydralazine can be used to treat brain cancer cells and maternal health.
“Preeclampsia has affected generations of women in my own family and continues to disproportionately impact Black mothers in the United States,” assistant chemistry professor Megan Matthews said to Penn Today. “Understanding how hydralazine works at the molecular level offers a path toward safer, more selective treatments for pregnancy-related hypertension.”
The researchers used hydralazine to treat glioblastoma cells for three consecutive days and found that the cells entered a stage where the tumor stopped growing. They found that the oxygen-sensing enzyme pathway also supports tumor cells to survive in low-oxygen environments. By suppressing the same pathway that signals to constrict blood vessels, hydralazine can prevent glioblastoma cells from growing.
“ADO [the oxygen-sensing enzyme] is like an alarm bell that rings the moment oxygen starts to fall,” Matthews said. “Most systems in the body take time; they have to copy DNA, make RNA, and build new proteins. ADO skips all that. It flips a biochemical switch in seconds.”
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The discovery is not only significant for brain cancer research, but it also serves to show how pre-existing medicines that have been safely used for decades can be useful to try to solve medical problems in completely separate areas.
“It’s rare that an old cardiovascular drug ends up teaching us something new about the brain,” Matthews said, “but that’s exactly what we’re hoping to find more of — unusual links that could spell new solutions.”
