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a scientist who studies existing phenomena blood pressure medicine This substance, called hydralazine, was discovered by chance to have the potential to fight cancer.
Hydralazine has been used to treat high blood pressure since the 1950s, but until now the exact mechanism of its action was unknown.
“This comes from the ‘pre-target’ era of drug discovery, when researchers first relied on what they observed in patients and then tried to explain the biology behind it,” Kyosuke Shishikura, a physician-scientist at the University of Pennsylvania who worked on the study, said in a press release from the university.
Shishikura and his extensive research team discovered that hydralazine directly targets a small but important enzyme called 2-aminoethanethiol dioxygenase (ADO).
This enzyme acts like a cell’s oxygen sensor, helping cells survive when oxygen levels drop. This helps enable fast-growing tumors like glioblastoma, which is a malignant tumor. brain tumor It resists treatment and most often relapses.
Hydralazine has been around since the 1950s and has traditionally been used to treat high blood pressure, but until now researchers didn’t understand exactly how it worked. (St. Petersburg)
In fast-growing cancers like glioblastoma, tumor cells multiply so quickly that the blood supply can’t keep up. This means that parts of the tumor are not receiving enough oxygen.
Normal cells die in low oxygen environments, but tumor cells It turns on a special survival system that helps it continue dividing even when oxygen is lacking. Studies have shown that one of those systems involves the ADO enzyme.
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“ADO is like an alarm bell that goes off the moment oxygen starts falling,” Megan Matthews, an assistant professor in the Department of Chemistry at the University of Pennsylvania and an investigator on the study, said in the same press release.
The research team used several advanced techniques, including X-ray crystallography, which analyzes the structure of the molecule, to examine how hydralazine binds to ADO.
Hydralazine binds to the enzyme ADO and stops its action. This shuts down the cell’s oxygen response system and, in the case of cancer cells, forces it to stop dividing. (St. Petersburg)
They discovered that hydralazine silenced the alarm by binding to ADO and stopping its action. This shuts down the cell’s oxygen response system. cancer cellsforce the split to stop.
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To test this finding, the research team treated human glioblastoma cells with hydralazine in the lab. After three days, they found that the cells had stopped growing and became larger and flatter. The cells entered a kind of permanent “sleep mode” known as “senescence,” the researchers said.
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The drug did not completely kill the cells, but it did take away their ability to grow and spread.
This is a major step forward in controlling cancers like glioblastoma, which are extremely difficult to treat and often recur even after treatment. surgery and chemotherapyaccording to Memorial Sloan Kettering Cancer Center.
While other cells die when deprived of oxygen, cancer cells adapt and continue to grow thanks to the ADO enzyme. (St. Petersburg)
Since hydralazine is already approved by the FDA, researchers hope they can reuse it. cancer treatment Much faster than new drugs.
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The researchers noted that previous experiments have only been carried out in cell cultures, and not yet in animals or humans. The next step is test Can ADO be safely and effectively blocked in biological systems?
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The press release emphasizes that this discovery is only a starting point for drug repurposing and has not yet led to clinical treatment.
As Matthews stated, “Understanding how hydralazine works at the molecular level provides a path to safer and more selective treatments.”
