Lab tests show it protects cells from UV radiation, inflammation and oxidative damage
Exemestane, a synthetic steroid drug widely prescribed to fight breast cancers that thrive on estrogens, not only inhibits the production of the hormone, but also appears to protect cells throughout the body against damage induced by UV radiation, inflammation and other assaults, according to results of research by Johns Hopkins scientists.
A summary of the research, performed on a variety of different animal and human cells, was published online in the Proceedings of the National Academy of Sciences on Nov. 4, and suggests that exemestane’s effectiveness against breast cancer could be due to more than its ability to halt estrogen production, the scientists say. The study’s results further imply that the drug, a so-called aromatase (estrogen synthesis) inhibitor, could potentially be prescribed more widely, including to men, as a way to counteract the wear and tear on cells that often leads to chronic diseases.
“Cells already have their own elaborate protective mechanisms, and in many cases they are ‘idling.’ The right drugs and foods can turn them on to full capacity,” says Paul Talalay, M.D., the John Jacob Abel Distinguished Service Professor of Pharmacology and Molecular Sciences at the Johns Hopkins University School of Medicine. “In our cell studies, we found that exemestane does exactly that,” he adds.
Talalay explains that cells are constantly under assault from a wide range of potentially lethal agents. UV radiation from the sun can cause errors in DNA sequences; reactive oxygen species — a class of unstable, oxygen-containing chemicals that are a natural byproduct of cellular functioning — can build up and cause damage to DNA and proteins; and ongoing inflammation can damage many essential cell functions.
To withstand the pressures against them, cells have evolved various mechanisms for protecting themselves. One involves turning on genes that produce a “SWAT team” of proteins, he notes, collectively called the phase 2 response. In normal cells, this response is not fully active. In previous work, the Talalay group found that sulforaphane, a chemical found in broccoli and other vegetables, can ramp up the phase 2 response and help protect cells from the constant wear and tear that they experience.
“Looking at the chemical structure of exemestane, I realized that it was similar to sulforaphane, and I wondered if it too could boost cells' phase 2 protective responses,” says Talalay.
To demonstrate that exemestane revs up the phase 2 response, Hua Liu, a research associate in Talalay’s laboratory, tested exemestane’s effects on various types of cells, including liver tumor and skin cells from a mouse, human cells from the eye’s retina, and rat heart cells. As expected, the addition of exemestane elevated the activity of typical protective phase 2 response enzymes in all of the cells tested, a result similar to the effects of adding sulforaphane.