Potential for added medical benefits uncovered for widely used breast cancer drug

November 7, 2013

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 , was published online in the Proceedings of the National Academy of Sciences on Nov. 4, and suggests that '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 , 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 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.

Exemestane was also effective in reducing the amount of reactive oxygen species in human retinal cells, where they are thought to contribute to age-related macular degeneration. It was also able to protect rat heart cells from similar damage.

To test the drug's ability to protect skin cells from UV-induced damage, Liu treated mouse skin cells with exemestane a day before subjecting them to UV radiation and, again, exemestane was able to protect the cells significantly, Liu and Talalay say.

Assessing exemestane's ability to protect cells from inflammation produced a surprise, Talalay notes. In all the other tests, Liu and Talalay had tried not only exemestane but also a mixture of exemestane and sulforaphane. They generally found that the two had an additive effect, suggesting that they both worked in a similar way and were more or less interchangeable. However, when mouse immune cells were exposed to both exemestane and sulforaphane, the two together were much more potent and at lower doses than either chemical alone.

"Our research showed unexpectedly that exemestane has multiple actions, which suggests that a wider use of exemestane should be considered if clinical tests confirm our cellular studies," says Talalay. "Of course, even if clinical tests confirm what we saw in , exemestane may not be appropriate for everyone. It's already advocated as a preventive measure for high-risk populations, but it may also be valuable in preventing other noncancerous chronic diseases."

Talalay notes that the drug is already approved by the U.S. Food and Drug Administration and taken by tens of thousands of women, with minimal side effects.

Explore further: Potential breast cancer prevention drug found to cause significant bone loss

More information: dx.doi.org/10.1073/pnas.1318247110

Related Stories

Potential breast cancer prevention drug found to cause significant bone loss

February 6, 2012
A drug that has been shown to prevent breast cancer in postmenopausal women at high risk of developing the disease, and is poised for widespread use, appears to significantly worsen age-related bone loss, according to an ...

Potential breast cancer prevention agent found to lower levels of 'good' cholesterol over time

December 9, 2011
Exemestane steadily lowered levels of "good" cholesterol in women taking the agent as part of a breast cancer prevention study, say researchers at Georgetown Lombardi Comprehensive Cancer Center. Exemestane, an aromatase ...

Circadian rhythms in skin stem cells protect us against UV rays

October 10, 2013
Human skin must cope with UV radiation from the sun and other harmful environmental factors that fluctuate in a circadian manner. A study published by Cell Press on October 10th in the journal Cell Stem Cell has revealed ...

Recommended for you

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.