Impact of estrogen metabolites on MCF-7 breast cancer cells: Insights from metabolomics study

Abstract

In addition to being highly stable, estrogen is widely available in the environment, food, and produce various metabolites such as 2-hydroxyestrone (2-OH-E1), 2-methoxyestrone (2-MeO-E1), etc., and they exert different hormonal effects in the human body. At present, estrone (E1) and estradiol (E2) have received more attention, but the role of estrogen metabolites has been neglected by the public. In this study, breast cancer cells were examined for their response to estrogen E1 and its metabolites using a cell model and metabolomics technology. Aims of the study included assessing the biological effects, studying structural effects on estrogen activity, analyzing metabolic changes in MCF-7 cells in response to estrogen exposure, and determining the correlation between estrogen effects and metabolic profiles. It was found that different structure of estrogen metabolites had different effects on MCF-7 cells. Treatment of cells with C-2 hydroxylated endogenous estrogen (2-OH-E1) resulted in a significant reduction of intracellular Ca2+ and reactive oxygen species (ROS), and the viability of cancer cells was inhibited by nearly 50%. Metabolomics results indicated that the specific differential metabolites induced by 2-OH-E1 were cis-aconitic acid, malic acid, lactobionic and L-methionine S-oxide. It is hypothesized that 2-OH-E1 can target cancer cells, interfere with TCA cycling and protein metabolism, and ultimately inhibit MCF-7 cancer cells. This discovery provides a new approach to the treatment of malignant breast tumors, enhances the understanding of estrogen metabolites, and raises awareness of the importance of metabolites.