{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:14:01Z","timestamp":1787026441297,"version":"build-2736575974"},"reference-count":81,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010937","name":"St. John's University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010937","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>\n                    As the most common cancer in women globally, breast cancer poses a significant public health concern. More concerning is its rising incidence rates in certain areas of the world, including Australia, New Zealand, Western Europe, and North America. Exposure to environmental endocrine-disrupting chemicals may play a role. One such chemical is atrazine (ATZ), a man-made herbicide highly prevalent in the environment and detectable in drinking water, with reported levels ranging from 0.026 to 1.29 micrograms per liter (\u00b5g\/L) in surface waters in the United States. During the development of breast cancer, many factors are involved, in particular the female sex hormone estrogen. Estrogen signaling fuels the proliferation and migration of estrogen receptor (ER)-positive breast cancer. The current review presents multiple lines of qualitative evidence from\n                    <jats:italic>in vitro<\/jats:italic>\n                    ,\n                    <jats:italic>in vivo<\/jats:italic>\n                    , and epidemiological studies connecting ATZ exposure to processes important for breast cancer development. Specifically, ATZ\u2019s stimulatory effect on breast cancer is mediated, at least partially, through enhanced CYP19A1 activity, the key enzyme converting testosterone to estradiol. ATZ stimulates CYP19A1 activity via parallel pathways, as evidenced by\n                    <jats:italic>in vitro<\/jats:italic>\n                    studies, potentially leading to elevated estradiol levels and estrogen signaling, which would then drive the development of ER-positive breast cancers. Beyond estrogen signaling, ATZ taps into the epidermal growth factor (EGF) signaling pathway to stimulate uncontrolled proliferation in human cell lines. We then show how curcumin, a phytochemical in turmeric, may counteract ATZ\u2019s effect on the aforementioned processes. Once curcumin passes through the ADME process and becomes available in the human body, curcumin may possess effects to counter ATZ\u2019s toxicity. Curcumin induces CYP3A4, as demonstrated by\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies, which catalyzes the degradation of steroid hormones, including estrogen. Curcumin downregulates the basal level of CYP19A1 in human cell lines via miRNA-125a and estrogen-related receptor alpha (ERR\u03b1), indicating an ability to dampen estrogen signaling. In addition, curcumin has been shown to inhibit the EGF receptor in human cell lines, thus blocking the EGF signaling cascade at the receptor level. Furthermore, curcumin may reduce ATZ\u2019s overall bioavailability. ATZ and its metabolites undergo glutathione (GSH) conjugation followed by renal excretion. Curcumin helps maintain the GSH pool and activates glutathione-S-transferase (GST) in rats, thereby potentially facilitating the detoxification and elimination of ATZ. In conclusion, we propose that curcumin\u2019s ability to induce CYP3A4, suppress CYP19A1, inhibit EGF signaling, and promote detoxification and elimination of ATZ makes curcumin a promising candidate for a mechanism-based antidote to ATZ toxicity.\n                  <\/jats:p>","DOI":"10.3389\/fendo.2025.1553465","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T04:13:41Z","timestamp":1753244021000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Curcumin as an antidote to atrazine on estrogen homeostasis and beyond: mechanistic insights from a targeted literature review"],"prefix":"10.3389","volume":"16","author":[{"given":"Patrick J.","family":"Wright","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jade","family":"Ilali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengli","family":"Bu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"B1","unstructured":"Breast cancer statistics\n          \n          London\n          World Cancer Res. Fund\n          \n          2025"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21754","article-title":"Breast cancer statistics, 2022","volume":"72","author":"Giaquinto","year":"2022","journal-title":"CA Cancer J Clin"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.25881","article-title":"Analysis of breast cancer mortality in the US\u20141975 to 2019","volume":"331","author":"Caswell-Jin","year":"2024","journal-title":"JAMA"},{"key":"B4","doi-asserted-by":"publisher","first-page":"19","DOI":"10.3892\/ol.2020.11566","article-title":"Endocrine disruptors from the environment affecting breast cancer (Review)","volume":"20","author":"Calaf","year":"2020","journal-title":"Oncol Lett"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2021.1903382","article-title":"Endocrine disrupting chemicals and breast cancer: a systematic review of epidemiological studies","volume":"62","author":"Wan","year":"2022","journal-title":"Crit Rev Food Sci Nutr"},{"key":"B6","unstructured":"Pesticides Industry Sales and Usage: 2008\u20132012 Market Estimates\n          \n          \n            \n              Atwood\n              D\n            \n            \n              Paisley-Jones\n              C\n            \n          \n          Washington, DC\n          US Environ. Prot. Agency\n          \n          2017"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.22004\/ag.econ.34011","article-title":"Atrazine: environmental characteristics and economics of management","author":"Ribaudo","year":"1994"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/etc.5037","article-title":"The atrazine saga and its importance to the future of toxicology, science, and environmental and human health","volume":"40","author":"Rohr","year":"2021","journal-title":"Environ Toxicol Chem"},{"key":"B9","unstructured":"Atrazine\n          \n          \n          \n          2025"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2022.113462","article-title":"Atrazine-induced oxidative damage via modulating xenobiotic-sensing nuclear receptors and cytochrome P450 systems in cerebrum and antagonism of lycopene","volume":"170","author":"Dai","year":"2022","journal-title":"Food Chem Toxicol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2134\/jeq2004.5940","article-title":"Measured concentrations of herbicides and model predictions of atrazine fate in the patuxent river estuary","volume":"33","author":"McConnell","year":"2004","journal-title":"J Env QUAL"},{"key":"B12","unstructured":"What Is Breast Cancer\n          \n          \n          \n          2021"},{"key":"B13","unstructured":"Types of Breast Cancer | About Breast Cancer\n          \n          \n          \n          2021"},{"key":"B14","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.mce.2017.08.011","article-title":"Estrogen and progesterone signalling in the normal breast and its implications for cancer development","volume":"466","author":"Hilton","year":"2018","journal-title":"Mol Cell Endocrinol"},{"key":"B15","unstructured":"Breast Cancer Hormone Receptor Status | Estrogen Receptor\n          \n          \n          \n          2021"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2011.05648.x","article-title":"Discovery of curcumin, a component of golden spice, and its miraculous biological activities","volume":"39","author":"Gupta","year":"2012","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2015.1077195","article-title":"Curcumin, an active component of turmeric ( Curcuma longa ), and its effects on health","volume":"57","author":"Kocaadam","year":"2017","journal-title":"Crit Rev Food Sci Nutr"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/foods6100092","article-title":"Curcumin: A review of its effects on human health","volume":"6","author":"Hewlings","year":"2017","journal-title":"Foods Basel Switz"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1055\/s-2006-957450","article-title":"Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers","volume":"64","author":"Shoba","year":"2007","journal-title":"Planta Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1021\/mp700113r","article-title":"Bioavailability of curcumin: problems and promises","volume":"4","author":"Anand","year":"2007","journal-title":"Mol Pharm"},{"key":"B21","unstructured":"Human Metabolome Database: Showing metabocard for Atrazine (HMDB0041830)\n          \n          \n          2022"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0184306","article-title":"Atrazine induced epigenetic transgenerational inheritance of disease, lean phenotype and sperm epimutation pathology biomarkers","volume":"12","author":"McBirney","year":"2017","journal-title":"PloS One"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2021.152761","article-title":"Atrazine impairs testicular function in BalB\/c mice by affecting Leydig cells","volume":"455","author":"Abarikwu","year":"2021","journal-title":"Toxicology"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1080\/10520295.2017.1310924","article-title":"Turmeric: old spice, new spice: Biotechnic & Histochemistry: Vol 92, No 5","volume":"92","author":"Cooksey","year":"2017","journal-title":"Biotech Histochem"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfr176","article-title":"Atrazine and breast cancer: A framework assessment of the toxicological and epidemiological evidence","volume":"123","author":"Simpkins","year":"2011","journal-title":"Toxicol Sci"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2023.114691","article-title":"Atrazine promotes breast cancer development by suppressing immune function and upregulating MMP expression","volume":"253","author":"Wang","year":"2023","journal-title":"Ecotoxicol Environ Saf"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1080\/15287399409531911","article-title":"Hypothesis for mammary tumorigenesis in Sprague-Dawley rats exposed to certain triazine herbicides","volume":"43","author":"Stevens","year":"1994","journal-title":"J Toxicol Environ Health"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1021\/pr900480f","article-title":"Effects of the endocrine disruptors atrazine and PCB 153 on the protein expression of MCF-7 human cells","volume":"8","author":"Lasserre","year":"2009","journal-title":"J Proteome Res"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.34297\/AJBSR.2019.04.000846","article-title":"Cell proliferative and cell cycle effects of atrazine using human breast cell lines","volume":"4","author":"Egiebor","year":"2019","journal-title":"Am J Biomed Sci Res"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3390\/ijms160714353","article-title":"Atrazine triggers DNA damage response and induces DNA double-strand breaks in MCF-10A cells","volume":"16","author":"Huang","year":"2015","journal-title":"Int J Mol Sci"},{"key":"B31","volume-title":"Conserved Molecular and Epigenetic Determinants of Aromatase Gene Induction by the Herbicide Atrazine in Human and Rat Cellular Models Relevant to Breast Cancer Risk","author":"Stueve","year":"2011"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2017.04.004","article-title":"In utero exposure to atrazine analytes and early menarche in the Avon Longitudinal Study of Parents and Children Cohort","volume":"156","author":"Namulanda","year":"2017","journal-title":"Environ Res"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-13-584","article-title":"Reproductive factors and risk of hormone receptor positive and negative breast cancer: a cohort study","volume":"13","author":"Ritte","year":"2013","journal-title":"BMC Cancer"},{"key":"B34","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1186\/s13058-018-1073-0","article-title":"Risk prediction for estrogen receptor-specific breast cancers in two large prospective cohorts","volume":"20","author":"Li","year":"2018","journal-title":"Breast Cancer Res"},{"key":"B35","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1038\/bjc.2011.254","article-title":"Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies","volume":"105","year":"2011","journal-title":"Br J Cancer"},{"key":"B36","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1097\/00001648-200011000-00005","article-title":"Age at menarche and tanner stage in girls exposed in utero and postnatally to polybrominated biphenyl","volume":"11","author":"Blanck","year":"2000","journal-title":"Epidemiology"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh292","article-title":"In utero exposure to organochlorines and age at menarche","volume":"19","author":"Vasiliu","year":"2004","journal-title":"Hum Reprod"},{"key":"B38","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1146\/annurev.physiol.64.081601.142703","article-title":"Aromatase\u2014A brief overview","volume":"64","author":"Simpson","year":"2002","journal-title":"Annu Rev Physiol"},{"key":"B39","article-title":"Aromatase research and its clinical significance","volume":"61","author":"Czajka-Oraniec","year":"2010","journal-title":"Endokrynol Pol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.9758","article-title":"Atrazine-induced aromatase expression is SF-1 dependent: implications for endocrine disruption in wildlife and reproductive cancers in humans","volume":"115","author":"Fan","year":"2007","journal-title":"Environ Health Perspect"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.02.062","article-title":"Herbicide atrazine activates SF-1 by direct affinity and concomitant co-activators recruitments to induce aromatase expression via promoter II","volume":"355","author":"Fan","year":"2007","journal-title":"Biochem Biophys Res Commun"},{"key":"B42","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.taap.2012.09.019","article-title":"Atrazine acts as an endocrine disrupter by inhibiting cAMP-specific phosphodiesterase-4","volume":"265","author":"Kucka","year":"2012","journal-title":"Toxicol Appl Pharmacol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2004.07.005","article-title":"Atrazine is a competitive inhibitor of phosphodiesterase but does not affect the estrogen receptor","volume":"154","author":"Roberge","year":"2004","journal-title":"Toxicol Lett"},{"key":"B44","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/j.steroids.2008.01.017","article-title":"Aromatase expression in the ovary: hormonal and molecular regulation","volume":"73","author":"Stocco","year":"2008","journal-title":"Steroids"},{"key":"B45","doi-asserted-by":"publisher","first-page":"8","DOI":"10.3785\/j.issn.1008-9292.2006.01.002","article-title":"Human pregnane X receptor-mediated transcriptional regulation of cytochrome P450 3A4 by some phytochemicals","volume":"35","author":"Liu","year":"2006","journal-title":"Zhejiang Xue Xue Bao Yi Xue Ban J Zhejiang Univ Med Sci"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/srep06587","article-title":"Oral intake of curcumin markedly activated CYP 3A4: in vivo and ex-vivo studies","volume":"4","author":"Hsieh","year":"2014","journal-title":"Sci Rep"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2011.12.009","article-title":"Controlled systemic delivery by polymeric implants enhances tissue and plasma curcumin levels compared with oral administration","volume":"80","author":"Bansal","year":"2012","journal-title":"Eur J Pharm Biopharm"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2024.117070","article-title":"Remission of copper-induced liver injury through the PXR\/NF-kB signaling pathway: The effects of dietary curcumin supplementation in largemouth bass (Micropterus salmoides)","volume":"285","author":"Li","year":"2024","journal-title":"Ecotoxicol Environ Saf"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2006.09.028","article-title":"Modulation of pregnane X receptor-and electrophile responsive element-mediated gene expression by dietary polyphenolic compounds","volume":"42","author":"Kluth","year":"2007","journal-title":"Free Radic Biol Med"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114508009847","article-title":"The effects of dietary curcumin and rutin on colonic inflammation and gene expression in multidrug resistance gene-deficient ( mdr1a\u2013\/\u2013 ) mice, a model of inflammatory bowel diseases","volume":"101","author":"Nones","year":"2008","journal-title":"Br J Nutr"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.toxlet.2018.07.023","article-title":"Essential oils of culinary herbs and spices activate PXR and induce CYP3A4 in human intestinal and hepatic in vitro models","volume":"296","author":"Bartonkova","year":"2018","journal-title":"Toxicol Lett"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10112686","article-title":"The role of CYP3A in health and disease","volume":"10","author":"Klyushova","year":"2022","journal-title":"Biomedicines"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1021\/tx970217f","article-title":"Roles of cytochromes P450 1A2 and 3A4 in the oxidation of estradiol and estrone in human liver microsomes","volume":"11","author":"Yamazaki","year":"1998","journal-title":"Chem Res Toxicol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1007\/s10552-011-9729-4","article-title":"Estrogens in the breast tissue: a systematic review","volume":"22","author":"Yaghjyan","year":"2011","journal-title":"Cancer Causes Control"},{"key":"B55","article-title":"Modulation of aromatase expression in the breast tissue by ERR1 orphan receptor","volume":"58","author":"Yang","year":"1999","journal-title":"Cancer Res"},{"key":"B56","article-title":"Transcriptional regulation of the estrogen-inducible pS2 breast cancer marker gene by the ERR family of orphan nuclear receptors","volume":"61","author":"Lu","year":"2001","journal-title":"Cancer Res"},{"key":"B57","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1002\/jcb.25612","article-title":"Curcumin promotes osteosarcoma cell death by activating miR-125a\/ERR\u03b1 Signal pathway","volume":"118","author":"Chen","year":"2016","journal-title":"J Cell Biochem"},{"key":"B58","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/1878-0261.12155","article-title":"Emerging functions of the EGFR in cancer","volume":"12","author":"Sigismund","year":"2018","journal-title":"Mol Oncol"},{"key":"B59","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.1038\/msb4100014","article-title":"A comprehensive pathway map of epidermal growth factor receptor signaling","volume":"1","author":"Oda","year":"2005","journal-title":"Mol Syst Biol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1172\/JCI15650","article-title":"What does Stat3 do","volume":"109","author":"Levy","year":"2002","journal-title":"J Clin Invest"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.1408586","article-title":"Effects of atrazine on estrogen receptor \u03b1\u2013 and G protein\u2013coupled receptor 30\u2013mediated signaling and proliferation in cancer cells and cancer-associated fibroblasts","volume":"123","author":"Albanito","year":"2015","journal-title":"Environ Health Perspect"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biomac.5b00229","article-title":"EGFR inhibition by curcumin in cancer cells: A dual mode of action","volume":"16","author":"Starok","year":"2015","journal-title":"Biomacromolecules"},{"key":"B63","first-page":"6438","article-title":"Curcumin inhibits oral squamous cell carcinoma proliferation and invasion via EGFR signaling pathways","volume":"7","author":"Zhen","year":"2014","journal-title":"Int J Clin Exp Pathol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1186\/s12906-016-1307-6","article-title":"Turmeric extract and its active compound, curcumin, protect against chronic CCl4-induced liver damage by enhancing antioxidation, BMC Complement","volume":"16","author":"Lee","year":"2016","journal-title":"Altern Med"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3791\/61347","article-title":"Spectrophotometric screening for potential inhibitors of cytosolic glutathione S-transferases","volume":"2020","author":"Robin","year":"2020","journal-title":"J Vis Exp"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.pestbp.2010.05.002","article-title":"Human metabolism of atrazine","volume":"98","author":"Joo","year":"2010","journal-title":"Pestic Biochem Physiol - PESTIC Biochem Physiol"},{"key":"B67","doi-asserted-by":"publisher","first-page":"61","DOI":"10.12988\/pacs.2014.411","article-title":"Curcumin restores glutathione-S-transferase activity for LNCaP prostate cancer cells","volume":"2","author":"Dubey","year":"2014","journal-title":"Pure Appl Chem Sci"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1080\/19440049.2011.580012","article-title":"Determination of atrazine and degradation products in Luxembourgish drinking water: origin and fate of potential endocrine-disrupting pesticides","volume":"28","author":"Bohn","year":"2011","journal-title":"Food Addit Contam Part A"},{"key":"B69","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.envres.2012.12.007","article-title":"Drinking-water exposure to a mixture of nitrate and low-dose atrazine metabolites and small-for-gestational age (SGA) babies: A historic cohort study","volume":"122","author":"Migeot","year":"2013","journal-title":"Environ Res"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.21574","article-title":"Modulatory effects of curcumin on redox status, mitochondrial function, and caspace-3 expression during atrazin-induced toxicity","volume":"28","author":"Keshk","year":"2014","journal-title":"J Biochem Mol Toxicol"},{"key":"B71","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-443-15840-7.00025-7","article-title":"Chapter 1 - Understanding pharmacotoxicology","volume-title":"Essent. Pharmatoxicology Drug Res","author":"Pawar","year":"2023"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2020.104660","article-title":"Regulating human safety: How dose selection in toxicity studies impacts human health hazard assessment and subsequent risk management options","volume":"114","author":"Woutersen","year":"2020","journal-title":"Regul Toxicol Pharmacol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-021-03155-4","article-title":"Principles of dose-setting in toxicology studies: the importance of kinetics for ensuring human safety","volume":"95","author":"Borgert","year":"2021","journal-title":"Arch Toxicol"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1002\/jat.1275","article-title":"Atrazine-induced changes in aromatase activity in estrogen sensitive target tissues","volume":"28","author":"Holloway","year":"2008","journal-title":"J Appl Toxicol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1042\/CS20140010","article-title":"Curcumin exerts inhibitory effects on undifferentiated nasopharyngeal carcinoma by inhibiting the expression of miR-125a-5p","volume":"127","author":"Gao","year":"2014","journal-title":"Clin Sci"},{"key":"B76","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1096\/fj.201700461RR","article-title":"miR-125a-3p inhibits ER\u03b1 transactivation and overrides tamoxifen resistance by targeting CDK3 in estrogen receptor-positive breast cancer","volume":"32","author":"Zheng","year":"2018","journal-title":"FASEB J Off Publ Fed Am Soc Exp Biol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1159\/000320570","article-title":"Reference profile correlation reveals estrogen-like trancriptional activity of curcumin","volume":"26","author":"Bachmeier","year":"2010","journal-title":"Cell Physiol Biochem"},{"key":"B78","article-title":"Curcumin inhibits endometriosis endometrial cells by reducing estradiol production","volume":"11","author":"Zhang","year":"2013","journal-title":"Iran J Reprod Med"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.31557\/APJCP.2020.21.4.1045","article-title":"Effect of Curcumin in Comparison with Trichostatin A on the Reactivation of Estrogen Receptor Alpha gene Expression, Cell Growth Inhibition and Apoptosis Induction in Hepatocellular Carcinoma Hepa 1\u20136 Cell lLine","volume":"21","author":"Sanaei","year":"2020","journal-title":"Asian Pac J Cancer Prev APJCP"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1159\/000099202","article-title":"The chemopreventive polyphenol curcumin prevents hematogenous breast cancer metastases in immunodeficient mice","volume":"19","author":"Bachmeier","year":"2007","journal-title":"Cell Physiol Biochem"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/20.6.1011","article-title":"Chemoprevention by curcumin during the promotion stage of tumorigenesis of mammary gland in rats irradiated with \u03b3-rays","volume":"20","author":"Inano","year":"1999","journal-title":"Carcinogenesis"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1553465\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T04:13:48Z","timestamp":1753244028000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1553465\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,23]]},"references-count":81,"alternative-id":["10.3389\/fendo.2025.1553465"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1553465","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,23]]},"article-number":"1553465"}}