Estrogenic, cytotoxic, proliferative effects of mycotoxins in human breast cancer cell line models: a systematic review

Objective To systematically review the estrogenic, proliferative, and cytotoxic effects of mycotoxins across human breast cell line models. Methods A systematic review was conducted across five primary databases, MEDLINE (via PubMed), Scopus, EMBASE, Web of Science, and Google Scholar, covering literature published up to December 2025 in adherence to PRISMA 2020 guidelines. Screenings were performed independently by two reviewers, and data regarding experimental models, exposure concentrations, durations, and phenotypic or mechanistic outcomes were systematically extracted. Results Forty-one studies spanning 20 mycotoxin classes across 11 cell lines revealed a clear receptor-dependent dichotomy. ER+ Models: Zearalenone (ZEN) and alpha-zearalenol acted as potent estrogen agonists. Alpha-zearalenol showed the highest relative proliferative potency (RPP = 7, normalized relative to 17β-estradiol assigned a reference baseline value of 1.0). TNBC/ER- Models: Lines were resistant to hormone-driven growth but highly vulnerable to cytotoxins. Aflatoxin B1 collapsed cell viability to 31.1% at 9.6 μg/mL. Gliotoxin (IC50: 38–985 nM) and Verrucarin A (IC50: 0.29–0.41 μM) displayed severe toxicity. Conclusion Mycotoxins exert diverse, receptor-dependent biological impacts rather than a uniform pharmacological effect. Dietary endocrine disruptors like ZEN act as potent environmental xenoestrogens in vitro , highlighting a strong mechanistic plausibility for tumor promotion in hormone-sensitive breast tissues. Future research must prioritize 3D organoids, co-exposure mixtures, and epidemiological tracking. However, given the predominantly medium risk of bias across the evaluated in vitro literature, these findings should be interpreted with methodological caution. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420261346524 ; https://osf.io/qh8w6/files/7kce6 .