Polyfluorinated iodine alkanes regulated distinct breast cancer cell progression through binding with estrogen...

Polyfluorinated iodine alkanes (PFIs) are a kind of emerging chemicals with endocrine disrupting effects. Based on the different binding preferences of PFIs to estrogen receptor alpha and beta isoforms (ERα and β), two representative PFIs, dodecafluoro-1,6-diiodohexane (PFHxDI) and tridecafluorohexyl iodide (PFHxI), were selected to evaluate their effects on the proliferation of two kinds of breast cancer cells with different ERα/β expression levels, MCF-7 and T47D. The cell viability assay showed PFHxDI could cause higher cellular toxicity than did PFHxI in both MCF-7 and T47D. MCF-7 with relatively higher ERα/β expression ratio was more vulnerable to the cytotoxic treatments of PFHxI and PFHxDI when compared with T47D cells with relatively lower ERα/β expression ratio. EdU incorporation and cell cycle analysis revealed that, similar to 17β-estrodiol (E₂), non-cytotoxic levels of PFHxDI could significantly promote the proliferation of MCF-7 by increasing cell population at S phase (p < 0.01), while T47D proliferation was not influenced by PFHxI exposure due to cell cycle arrest at G2/M phase. The cellular responses caused by estrogenic PFIs were dominantly mediated by their preferential binding affinities for ER isoforms, which would be helpful in the accurate assessment for their potential influences on the breast cancer progression.