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Peer-reviewedCC BY 4.0Frontiers in Public Health

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

Abstract

ObjectiveTo systematically review the estrogenic, proliferative, and cytotoxic effects of mycotoxins across human breast cell line models.MethodsA 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.ResultsForty-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.ConclusionMycotoxins 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 registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420261346524; https://osf.io/qh8w6/files/7kce6.

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BibTeX
@article{sasidharan2026estrogenic,
  title = {{Estrogenic, cytotoxic, proliferative effects of mycotoxins in human breast cancer cell line models: a systematic review}},
  author = {Sivakumar Sasidharan and Piplani Naina and Dubey Jyoti and Taruna Arora and Archana Burman and Savita Bansal and Sivakumar Gowardhan and Abha Mishra and Nilesh Chandra},
  journal = {Frontiers in Public Health},
  year = {2026},
  month = oct,
  doi = {10.3389/fpubh.2026.1950615},
  url = {https://www.frontiersin.org/articles/10.3389/fpubh.2026.1950615},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Estrogenic, cytotoxic, proliferative effects of mycotoxins in human breast cancer cell line models: a systematic review
AU  - Sivakumar Sasidharan
AU  - Piplani Naina
AU  - Dubey Jyoti
AU  - Taruna Arora
AU  - Archana Burman
AU  - Savita Bansal
AU  - Sivakumar Gowardhan
AU  - Abha Mishra
AU  - Nilesh Chandra
PY  - 2026
DA  - 2026/10/30
JO  - Frontiers in Public Health
DO  - 10.3389/fpubh.2026.1950615
UR  - https://www.frontiersin.org/articles/10.3389/fpubh.2026.1950615
AB  - ObjectiveTo systematically review the estrogenic, proliferative, and cytotoxic effects of mycotoxins across human breast cell line models.MethodsA 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.ResultsForty-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.ConclusionMycotoxins 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 registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420261346524; https://osf.io/qh8w6/files/7kce6.
SN  - 2296-2565
ER  -