The Effect of Metalloestrogens on the Effectiveness of Aromatase Inhibitors in a Hormone-Dependent Breast Cancer Cell Model

SIMPLE SUMMARY: Progressive industrialization, urbanization, and consumerism lead to increased contamination of the environment with endocrine-disrupting compounds (EDCs) which play an important role in the increased incidence of hormone-dependent cancers, e.g., breast cancer. EDCs include, among others, xenoestrogens—exogenous compounds that can bind to estrogen receptors and thus compete with, or mimic the action of endogenous estrogens (e.g., promote the proliferation of cancer cells). The aim of the study was to answer the question whether exposure to selected xenoestrogens, widespread in everyday life (aluminum in antiperspirants and deodorants; chromium (III) in dietary supplements and drugs) affects the effectiveness of drugs used in hormone therapy in breast cancer. We performed in vitro tests on a breast cancer cell model—MCF-7 and MCF-7/DOX cell lines exposed to selected xenoestrogens, drugs, and their combinations. Our results confirm that such exposure may negatively affect the effectiveness of breast cancer hormone therapy. ABSTRACT: Endocrine-disrupting compounds (EDC) play an important role in the increased incidence of breast cancer (BC). There are some 160 xenoestrogens that may be involved in the development of BC. Much less is known about the influence of xenoestrogens on the effectiveness of the treatment of BC. The aim of this study was to analyze the interaction of metalloestrogens (aluminum and chromium (III)) and drugs used in the treatment of hormone-dependent BC—aromatase inhibitors (AI)—letrozole and exemestane. A cell viability assay, a flow cytometer analysis of apoptosis and cell cycle phases, and protein activity of BAX and Bcl-2 were performed on two human breast cancer cell lines—MCF-7 and MCF-7/DOX. In MCF-7 cells, the lower concentration of exemestane and higher of letrozole, in combination with metalloestrogens, results in a decrease in the effectiveness of drugs. Additionally, in the MCF-7/DOX cell line, we observed that the combination of metalloestrogens and AI leads to a decrease in the drug’s effectiveness due to an increase in the viability of breast cancer cells (both concentrations of letrozole and higher concentration of exemestane). In both cell lines, the reduction in the effectiveness of AI, in combination with metalloestrogens, is not related to the influence on the cell cycle. Our results confirm that exposure to metalloestrogens may negatively affect the effectiveness of hormone therapy with AI. Further studies are needed to fully explain the mechanism of these interactions.