When cells in the human body age incorrectly, this can sometimes make it easier for cancer to develop or spread. For this reason, scientists are looking for new drugs able to act on processes that relate to cell aging. But could an existing drug come in handy?
Cellular aging — that scientists call senescence — is a natural process that allows the body to filter out old and damaged cells that no longer fulfill their purpose.
However, senescence sometimes malfunctions, and some researchers believe that this can contribute to the growth and spread of cancer tumors.
Thus, specialists have been hard at work to find new drugs, which they term senolytics, that can kill senescent cells that may pose a threat to health.
Previous studies in animal models have shown that senolytics could have a number of benefits, including keeping individuals healthier for longer and prolonging life span.
And some senolytics, such as navitoclax, have demonstrated some effectiveness in treating blood cancers, including leukemia and lymphoma. Yet navitoclax can also have serious side effects, including thrombocytopenia, or abnormally low platelet levels in the blood.
Recently, however, researchers from the MRC London Institute of Medical Sciences in the United Kingdom may have identified an alternative senolytic — in the form of an existing heart drug known as ouabain.
In the study paper that appears in the journal Nature Metabolism, the investigators explain that they experimented with various existing drugs, testing them on both healthy and senescent cells to see how they would act.
In doing so, they closed in on ouabain, a compound that forms part of the same class of drugs as digoxin and digitoxin, namely cardiac glycosides. Such compounds can treat heart conditions, including cardiac arrhythmias and atrial fibrillation, both of which have characteristics of irregular or abnormal heartbeats.
The research team found that ouabain can selectively kill different types of aging cells, including those that have become senescent because of cancer, or due to exposure to radiotherapy or chemotherapy, including treatments with drugs such as etoposide and doxorubicin.
This makes ouabain a potential candidate for use as a broad spectrum senolytic: a drug that targets a very varied array of aging cells.
The researchers reached this conclusion by testing the drug in vivo, in aging mice, and “in precancerous lesions in the liver and upon radiotherapy,” as senior author Prof. Jesús Gil explains.
Prof. Gil and colleagues also point out that the fact that it is already readily available makes further research using this drug easier.
“These drugs are already used in the clinic, so they could be repurposed to treat a long list of diseases, including cancer. This is something we are keen to explore with our clinical collaborators.”
Prof. Jesús Gil
“Moreover,” the senior author adds, “many patients are being treated with digoxin, and an epidemiologist could look retrospectively and ask the question of whether those patients who were treated with digoxin are doing better than those who weren’t.”
Thus, future studies could compare the health outcomes for people who have received treatment with cardiac glycosides versus those who have not, making it easier to confirm whether this class of drugs has true potential as a senolytic.