Researchers develop screening assay that quickly assesses nearly 1,500 compounds' effect on estrogen

Feb 20 2014

A team of researchers at City of Hope has developed a screening assay that can quickly assess up to 1,536 compounds' effect on estrogen activity in the body. The test can also evaluate whether chemicals act as inhibitors of aromatase, an enzyme linked to breast cancer that converts androgen to estrogen.

The results verifying this novel screening method—called AroER tri-screenTM—are published ahead of print online in Toxicological Sciences. The test can screen for more than 1,500 compounds with each run, enabling scientists to rapidly assess and identify the estrogen-disrupting impact of common chemicals. Even everyday chemicals have the potential to increase, or potentially decrease, the risk of breast cancer, researchers say.

"Approximately 70 percent of breast cancers are sensitive to estrogen, and exposure to estrogen-disrupting compounds — especially during the critical periods of pregnancy, childhood and adolescence — can have an irreversible impact on still-developing bodies," said Shiuan Chen, Ph.D., professor and chair of City of Hope's Department of Cancer Biology and lead author of the study. "Thus, it makes sense to develop this test, which can assess many chemicals at once, to help us quickly identify which environmental compounds are disrupting estrogen functions."

The screening method uses a microplate, a special plate containing miniature test tubes known as wells. In the wells are specially cultured estrogen-sensitive breast cancer cells treated to detect either estrogen-promoting or estrogen-suppressing properties of chemicals. The researchers collaborated with the Tox-21 program (a national effort to develop methods to screen for hazardous chemicals) to amplify the number of wells in the microplate — from the original 96 to 1,536 — greatly increasing the number of assessments each test can process.

In addition to confirming AroER tri-screen's effectiveness, the researchers found that antifungal medications oxiconazol (Oxistat) and bifonazole (Canespor) exhibited aromatase-inhibiting properties, while the antidepressant paroxetine (Paxil) acted as an estrogen promoter.

"The paroxetine finding helps explain previous studies showing that it reduces tamoxifen therapy's effectiveness," Chen said. "And it has implications for patients with estrogen-sensitive breast cancer who are on other medications."

Meanwhile, the oxiconazol and bifonazole findings mean that these drugs may have potential in treating estrogen-sensitive breast cancers by inhibiting aromatase and thus levels of estrogen in the body.

Given these promising findings, Chen said that he hopes the AroER tri-screenTM assay will be be used to assess the estrogen-disrupting properties of more compounds, including medications, environmental pollutants and common household chemicals.

The project was supported by the California Breast Cancer Research Program (17UB-8701) with the goal to develop such a screening system to identify environmental chemicals with impact on breast cancer development. Other researchers involved in this study include Dujin Zhou, Ph.D., Li-Yu Hsin, M.S., Noriko Kanaya, Ph.D., Cynthie Wong, Ph.D., Yate-Ching Yuan, Ph.D., and Richard Yip, Ph.D. from City of Hope and Srilatha Sakamuru, Ph.D., Menghang Xia, Ph.D., Kristine Witt, Ph.D., and Christina Teng, Ph.D., from the National Institutes of Health. Research reported in this publication included work performed in the Bioinformatics Core, High Throughput Screening Core and Integrative Genomics Core supported by the National Cancer Institute of the National Institutes of Health under award number P30CA33572.

Source: City of Hope