Screening assay can assess impact of 1536 compounds on estrogen levels
Researchers at City of Hope (CA, USA) have developed a novel screening assay, named AroER tri-screen™, which allows the effect of up to 1536 compounds on estrogen levels to be rapidly assessed. Compounds that interfere with the biosynthesis, metabolism and functions of estrogen can influence the development of breast cancer. AroER tri-screen uses a microplate with wells that contain breast cancer cells. These cells are cultured to identify estrogen-promoting or estrogen-suppressing properties of compounds via estrogen-responsive elements.
The study, recently published in Toxicological Sciences, describes how the team screened 446 drugs in the NIH Clinical Collection and detected 106 that modulate estrogen levels. For example, the antidepressant paroxetine was found to be an estrogen promoter. In addition to detecting estrogen receptor agonists and/or antagonists, the assay can also detect inhibitors of aromatase – an enzyme linked to breast cancer that converts androgen to estrogen. The team identified two antifungal medications that exhibit aromatase-inhibiting properties, and therefore may have potential in treating estrogen-sensitive breast cancers.
Lead author of the study, Shiuan Chen, commented, “Approximately 70% 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.” Chen continued, “The paroxetine finding helps explain previous studies showing that it reduces tamoxifen therapy’s effectiveness, and it has implications for patients with estrogen-sensitive breast cancer who are on other medications.”
In light of these promising findings, Chen hopes that the assay will be used to rapidly identify compounds that disrupt estrogen functions, including medications, environmental pollutants and common household chemicals.
Sources: City of Hope researchers develop test to assess effect of more than 1500 chemicals on estrogen; Chen S, Zhou D, Hsin LY et al. AroER Tri-Screen™ is a biologically relevant assay for endocrine disrupting chemicals modulating the activity of aromatase and/or the estrogen receptor. Toxicol. Sci. DOI: 10.1093/toxsci/kfu023 (2014) (Epub ahead of print).
