The estrogenic and anti-estrogenic effects of butylparaben (BuPB), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and propyl gallate (PG) were evaluated for individual compounds as well as for binary mixtures, using an estrogen-dependent reporter gene assay in T47D-Kbluc breast cancer cells and an estrogen-dependent proliferation assay in MCF-7 breast cancer cells. In terms of estrogenicity the potency of the selected compounds increased from BHA < PG < BuPB in the luciferase assay (with BHT showing no significant estrogenic activity), while in the proliferation assay the following order was observed: BHT < BHA < BuPB (with PG showing no significant estrogenic activity). Non-monotonic dose-response curves were obtained for BuPB (in both assays) and PG (in the luciferase assay), respectively. In the presence of estradiol, a significant anti-estrogenic activity was observed in both cell lines for PG, BuPB and BHA, while BHT showed weak anti-estrogenic activity only in T47D-Kbluc cells. The evaluation of binary mixtures confirmed the endocrine disruptive potential of the compounds, their individual potency being correlated with that of the mixtures. All mixtures were able to reduce the estradiol-induced luminescence or cell proliferation, an effect that was accurately predicted by the dose addition mathematical model, suggesting the same (or at least partially overlapping) modes of action for the tested compounds. The results of the present study emphasize the importance of a cumulative risk assessment of endocrine disruptors.
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http://dx.doi.org/10.1002/jat.3601 | DOI Listing |
Biochem Pharmacol
November 2024
Department of Physiology, Nippon Medical School, Bunkyo-ku, Tokyo 113-8602, Japan.
This comprehensive review of estrogenic alkaloids reveals that although the number is small, they exhibit a wide range of structures, biosynthesis pathways, mechanisms of action, and applications. Estrogenic alkaloids belong to different classes, different biosynthetic pathways, different estrogenic actions (estrogenic/synergistic, anti-estrogenic/antagonistic, biphasic, and acting as a selective estrogen receptor modulator or SERM), different receptor-initiated signaling pathways, different ways of modulations of estrogen action, and different applications. The future applications of estrogenic alkaloids, such as those for diagnostics, drug development, and therapeutics, are considered with the help of new databases containing comprehensive descriptions of their relationships and more elaborate artificial intelligence-based prediction technologies.
View Article and Find Full Text PDFFood Chem
February 2025
Department of Food Science and Technology, Graphic Era (Deemed to be University), Dehradun, Uttarakhand 248002, India. Electronic address:
Phytoestrogens, derived from plants possesses structural similarity with 17 β-estradiol found in mammals. It is abundantly present in soybean along with red clove, alfalfa as well as other legumes, nuts, vegetables and seeds. It is used as hormone replacement therapy and exhibits both anti-estrogenic and estrogenic properties that linked to therapeutic benefits as well as plays active role in sports nutrition.
View Article and Find Full Text PDFFEBS Open Bio
September 2024
General Directorate of Poison Control Centre, Ministry of Health, Riyadh, Saudi Arabia.
Concerns regarding man-made organic chemicals pervading our ecosystem and having adverse and detrimental effects upon organisms, including man, have now been studied for several decades. Since the 1970s, some environmental pollutants were identified as having endocrine disrupting affects. These endocrine disrupting chemicals (EDC) were initially shown to have estrogenic or anti-estrogenic properties and some were also shown to bind to a variety of hormone receptors.
View Article and Find Full Text PDFInt J Mol Sci
August 2024
Institute for Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
Anti-estrogenic therapy is established in the management of estrogen receptor (ER)-positive breast cancer. However, to overcome resistance and improve therapeutic outcome, novel strategies are needed such as targeting widely recognized aberrant epigenetics. The study aims to investigate the combination of the aromatase inhibitor exemestane and the histone deacetylase (HDAC) inhibitor and antioxidant α-lipoic acid in ER-positive breast cancer cells.
View Article and Find Full Text PDFJ Steroid Biochem Mol Biol
October 2024
Department of Biochemistry, Stellenbosch University, Van de Byl Street, Stellenbosch, 7601, South Africa.
Despite being the focal point of decades of research, female breast cancer (BC) continues to be one of the most lethal cancers in the world. Given that 80 % of all diagnosed BC cases are estrogen receptor-positive (ER+) with carcinogenesis driven by estrogen-ERα signalling, current standard of care (SOC) hormone therapies are geared towards modulating the function and expression levels of estrogen and its receptors, ERα and ERβ. Currently, aromatase inhibitors (AIs), selective ER modulators (SERMs) and selective ER degraders (SERDs) are clinically prescribed for the management and treatment of ER+ BC, with the anti-aromatase activity of AIs abrogating estrogen biosynthesis, while the anti-estrogenic SERMs and SERDs antagonise and degrade the ER, respectively.
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