Old Blood Pressure Drug May Hold the Key to Halt Aggressive Brain Cancer Growth
A 70-year-old medical mystery surrounding a vital blood pressure medication, hydralazine, has finally been solved. Not only do scientists now understand how it works at the molecular level – which offers important clues to help chemically improve the drug for patients with hypertension or to treat preeclampsia during pregnancy – but it also has the potential to prevent the growth of brain tumors.
A collaboration between universities across the United States is described in a study published in Scientific advances how cells in the most aggressive form of hydralazine-treated brain cancer became dormant. This shows that sometimes, instead of inventing new treatments from scratch, we just need to look at what we already have from a different perspective.
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The mechanisms of action of drugs are often poorly understood
As one of the World Health Organization’s most essential medicines, hydralazine entered the market 70 years ago to treat high blood pressure and preeclampsia, a pregnancy-related blood pressure condition that accounts for about 10 percent of maternal deaths worldwide, according to the World Health Organization.
Despite its success, researchers weren’t sure how hydralazine worked its magic – and it wasn’t the only one. Before the 1980s, many drugs were approved based solely on clinical observations, and only later did scientists “try to explain the biology of them,” Kyosuke Shishikura, a physician-scientist at the University of Pennsylvania, said in a press release.
In their study, the research team ultimately identified hydralazine’s targets at the molecular level. They found that it blocks an oxygen-sensing enzyme called 2-aminoethanethiol dioxygenase (ADO), which normally signals blood vessels to contract based on oxygen levels, causing blood pressure to rise.
Hydralazine prevents aggressive brain cancer from growing
But how does brain cancer come into play? Cancer researchers have long suspected that ADO plays an important role in one of the most aggressive forms of brain cancer, glioblastoma, due to its low-oxygen environment. ADO levels appear to increase as the tumor becomes aggressive, but no effective ADO inhibitors have been known to confirm this theory.
Using a high-resolution imaging technique called X-ray crystallography, biochemists at the University of Texas were able to show that hydralazine interacts with ADO, leading to further testing in brain cancer cells. In vitro, hydralazine treatment caused tumor cells to enter senescence – a dormant state in which cells stop growing. Compared to chemotherapy, this approach works more selectively, potentially causing fewer side effects.
Improving an old cardiovascular drug
Finally, discovering the biochemical mechanism not only benefits new treatment options, but also allows researchers to refine hydralazine for its original use: treating high blood pressure.
“Understanding how hydralazine works at the molecular level opens the way to safer and more selective treatments for pregnancy-related hypertension, potentially improving outcomes for patients most at risk,” Kyosuke explained.
Findings like this are prompting scientists to reconsider long-established treatments that may have surprising therapeutic potential for other medical challenges. The next steps are to refine the chemistry to design safer, more specific and effective ADO inhibitors that can cross the blood-brain barrier to reach their target.
“It’s rare that an old cardiovascular drug ends up teaching us something new about the brain,” Megan Matthews, study co-author and assistant professor at the University of Pennsylvania, said in the press release, “but that’s exactly what we hope to find more of: unusual connections that could provide new solutions.”
This article does not offer medical advice and should be used for informational purposes only.
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