Researchers exploring a blood pressure medication known as hydralazine stumbled upon its potential role in combating cancer. Initially used since the 1950s to treat hypertension, the specific way hydralazine functions had remained unclear.
Kyosuke Shishikura, a physician-scientist from the University of Pennsylvania involved in the research, explained that this finding reflects the earlier days of drug discovery, where observations in patients sparked scientific inquiry.
Shishikura and his team concluded that hydralazine directly affects a crucial enzyme called 2-aminoethanethiol dioxygenase (ADO). This enzyme helps cells manage low oxygen environments, facilitating tumor growth in aggressive cancers like glioblastoma, which is known for its resistance to treatment and high recurrence rate.
In rapidly growing tumors, blood flow often can’t keep pace, leading to low oxygen levels within parts of the tumor. While normal cells perish in these conditions, cancer cells activate survival mechanisms, and this includes the ADO enzyme.
“ADO essentially acts as an alarm, signaling when oxygen levels drop,” remarked Megan Matthews, an assistant professor in the Department of Chemistry at the University of Pennsylvania who co-authored the study.
Utilizing various advanced methods, including X-ray crystallography, the team investigated how hydralazine interacts with ADO. They discovered that it effectively silences the alarm by binding to ADO, disrupting its function. This, in turn, inhibits the oxygen response system and hinders cancer cell division.
In laboratory tests involving human glioblastoma cells, the researchers found that after three days of being treated with hydralazine, the cancer cells ceased to grow and adopted a larger, flatter appearance, effectively entering a state known as “senescence,” whereby they could no longer proliferate.
Although the drug did not eliminate the cells, it significantly impaired their growth and spread. This represents a vital advancement in managing challenging cancers like glioblastoma, which often proves tough to treat and tends to reappear after conventional therapies.
Fortunately, since hydralazine is already approved by the FDA, there is hope that it can be quickly repurposed for cancer treatment compared to developing entirely new drugs.
However, the researchers pointed out that their experiments so far have been limited to cell cultures. They plan to test the effectiveness and safety of blocking ADO in living organisms next. The findings are still early, and while promising, they have yet to translate into clinical practice.
As Matthews noted, “A deeper understanding of how hydralazine functions at a molecular level could pave the way for safer, more focused treatment options.”
