Fenhexamid (Fen) is used to eradicate gray mold of fruits and vegetables leading to greater detection of its residual concentration in wine than other fungicides. Here, we further investigated the malign influence of Fen on the migration and angiogenesis via regulation of the
estrogen receptor (ER) and
phosphoinositide 3-kinase (PI3K) pathways in
breast cancer models. ER-positive MCF-7 and ER-negative MDA-MB-231
breast cancer cells were exposed to 17β-estradiol (E2, 10-9 M), Fen (10-5 M and 10-7 M),
ICI 182,780 (ICI; an ER antagonist, 10-8 M) or/and
Pictilisib (Pic; a PI3K inhibitor, 10-7 M), and subsequently subjected to migration assay, live cell motility monitoring, trans-chamber assay, immunofluorescence, angiogenesis assay,
tumor spheroid formation, and Western blot analysis. In MCF-7 cells, E2 and Fen induced cell migration by regulating the cell migration-related
proteins. Although expressions of
N-cadherin and
Vimentin remained unchanged E2 and Fen induced the decrease of
E-cadherin and
Occludin in the immunofluorescence assay and Western blot analysis. In addition, Fen increased vessel formation in HUVEC cells. Furthermore, Fen treatment induced the formation of larger and denser
tumor spheroids in MCF-7 cells. Western blot further confirmed the increased expressions of
vascular endothelial growth factor (
VEGF) and sex-determining region Y-box 2 (SOX2) after exposure to Fen. We conclude that Fen plays an important role as an
endocrine-disrupting chemical in
breast cancer migration and
metastasis through the regulation of ER and PI3K signaling pathways.