Bisphenol TMC exhibits greater estrogenic activity than Bisphenol A and three other structural analogues exemplified by higher estrogen receptor α-mediated gene expression and breast cancer cell proliferation.
Level 5 - mechanism / opinion, no new human data
In vitro cell culture and in silico mechanistic bench research without human or animal in vivo data.
PubMed 41482203 · doi:10.1016/j.tox.2025.154393
What was done
The authors assessed the estrogenic activity of bisphenol A (BPA) and four understudied structural analogues (cyclo-di-BADGE, TBBPS, BPSIP, and BPTMC). They conducted estrogen receptor alpha (ERα) transactivation assays in HEK-293 cells, in silico molecular modeling, and enzyme inhibition assays for 17β-HSD1 and 17β-HSD2. In ERα-positive MCF-7 breast cancer cells, they evaluated target gene expression (GREB1, TFF1, PGR) after 24-hour exposure to 1 µM BPTMC and measured cell proliferation over 72 hours, testing reversibility with the ERα antagonist fulvestrant.
What was found
BPTMC showed greater ERα agonistic potency than BPA in HEK-293 cells, with an EC50 of 87 ± 20 nM compared to 400 ± 100 nM for BPA, whereas the other analogues showed no significant agonistic activity. BPTMC selectively inhibited 17β-HSD2 (IC50 = 4.8 ± 0.6 µM), unlike BPA, but neither compound inhibited 17β-HSD1. In MCF-7 cells, 1 µM BPTMC upregulated GREB1, TFF1, and PGR expression to levels comparable to 10 nM E2, an effect blocked by 100 nM fulvestrant. BPTMC also stimulated MCF-7 proliferation at nanomolar concentrations over 72 hours, which was fully reversed by fulvestrant.
Why it matters
This study shows that BPTMC is a more potent ERα agonist than BPA and can drive breast cancer cell proliferation at nanomolar concentrations. The findings demonstrate that substituting BPA with understudied structural analogues may introduce chemicals with greater endocrine-disrupting potential.
Limits
The study is entirely in vitro (HEK-293 and MCF-7 cell models) and in silico, lacking in vivo pharmacokinetic, metabolic, or animal toxicity data. Real-world human exposure levels, bioavailability, and tissue accumulation for BPTMC were not evaluated.
Cited by
- supports BPA acts as an estrogen mimic in the body.