Researchers from Georgetown University have found that combining a drug used for epilepsy, bipolar disorder, and migraines with a drug used to ease blood pressure may be able to reverse some aspects of breast cancer.
In their study, the researchers found the drug combination to be effective in reversing some aspects of breast cancer in mice at a high risk of the disease due to their mothers ingesting a high fat diet during pregnancy. The researchers also found that when mothers were not fed a high fat diet during pregnancy, the drug combination increased their offspring’s chances of developing breast cancer.
In particular, valproic acid was studied, which, among multiple targets, inhibits the production of histone deacetylase (HDAV), epigenetic silencer of genes. Combined with blood pressure drug hydralazine, that inhibits epigenetic regulator DNA methyltransferase (DNMT), the two drugs were found to work in tandem and disrupt the growth of tumors.
Leena A. Hilakivi-Clarke, oncology professor at Georgetown University said, “We believe that our research is the first to show that we can reverse some aspects of increased breast cancer risk found in offspring of mouse mothers fed a high fat diet during pregnancy...This finding may have important implications in people because exposures in the womb to certain chemicals, or a mother's high fat diet, or being obese, can subsequently increase a daughter's breast cancer risk."
In particular, the findings show the impact epigenetic methyl group addition or subtraction can have on disease risk factors. Compounds that reduce methylation of excessively methylated (hypermethylated) tumor suppressor genes can help stave off cancer later on. Meanwhile, for tumor suppressor genes that are not hypermethylated, the same compounds have the opposite effect. Removing methyl groups from cancer-causing genes, they become more active and thus more likely to develop into aggressive cancers.
The findings from the study also suggest a different approach to diets. For example, many fruits and vegetables have compounds that react similarly to HDAC and DNMT inhibiting drugs. Thus, the research suggests that consumption of these foods may have a protective benefit against a high breast cancer risk caused by exposure to a high fat diet while in the womb. Conversely, as folic acid has the opposite effect, it may provide protection against cancer for those not exposed to a high fat diet while in the womb.
Hilakivi-Clarke said, “Our next step will be to try to identify biomarkers in humans that indicate an exposure in the womb to diets or endocrine disrupting chemicals that could increase breast cancer risk later in life...If we can identify such biomarkers, we'll look to see if specific foods consumed by women can reverse epigenetic changes to their DNA that might lead to increased breast cancer risk."