In an accidental discovery where scientists were studying a common blood pressure drug called hydralazine, found out that it could in fact, fight cancer. What Is Hydralazine?Most commonly known by its brand name Apresoline, Hydralazine is a prescription medication, which is mainly used to treat high blood pressure or hypertension and heart failure. It works as a direct-acting vasodilator that relaxes the blood vessels, and allows blood to flow more easily and reduce the heart's workload. This drug is commonly consumed orally and is prescribed by a GP to be taken two to four a day, depending on the severity of one's case. However, the drug can only control blood pressure, and not cure it. It is also used after heart valve replacement and in the treatment of heart failure. Does Hydralazine, A Common Blood Pressure Drug Fight Cancer?Kyosuke Shishikura, a physician-scientist at the University of Pennsylvania along with a wider research team uncovered that hydralazine directly targets a small, but a crucial enzyme called 2-aminoethanethiol dioxygenase (ADO). In a press release, Shishikura said, "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."So, How does This Common Blood Pressure Drug Work To Fight Cancer?The enzyme acts like a cellular oxygen sensor and helps the cells survive even when the oxygen levels are low. This can thus help enable the fast-growing tumors like glioblastoma, which is an aggressive form of brain cancer that resists treatment and almost always comes back. What Happens In A Fast-growing Cancer Like Glioblastoma?In glioblastoma, the tumor cells multiply rapidly and the blood supply therefore cannot keep up. This means parts of tumor do not get enough oxygen. While the typical cells die in low-oxygen environment, a tumor cell could switch on its survival system that could help them continue to survive even when the oxygen is scarce. This also involved the ADO enzyme. In the same press release Megan Matthews, who is an assistant professor in Penn's Department of Chemistry and a researcher in the study said, "ADO is like an alarm bell that rings the moment oxygen starts to fall." How Did The Research Team Approach This Study?The team used advanced techniques, which also included X-ray crystallography, which analyzes the structure of molecules to determine how hydralazine binds to ADO. The researchers discovered that hydralazine silences that alarm by binding ADO and making it stop working, which means the tumor cells will not be able to survive even when the oxygen is low. This, as the researchers explained, in turn, shuts down the cell's oxygen response system, and forces the cancer cells to stop dividing them. Was This Theory Of Common Blood Pressure Drug Fighting Cancer Tested?The scientists tested this theory on human glioblastoma cells with hydralazine in the lab. After three days, they found out that the cells had stopped multiplying and became larger and flatter. The cell entered, what the scientists called a permanent "sleep mode", which is known as "senescence".However, it is important to note that the drug did not kill the cells, but it took away the cell's ability to grow and spread. As per Memorial Sloan Kettering Cancer Center, this is a huge step towards controlling cancers like glioblastoma, as they are extremely difficulty to treat, and they often return even after surgery and chemotherapy. The good news is that budralazine is already FDA-approved, and researchers are hoping that this drug could reshape the cancer therapy.
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