Oestrogenic and androgenic activity of triclosan in breast cancer cells.
As a consequence of its widespread use as an antimicrobial agent in consumer goods, triclosan has become distributed ubiquitously across the ecosystem, and recent reports that it can cause endocrine disruption in aquatic species has increased concern. It is reported here that triclosan possesses intrinsic oestrogenic and androgenic activity in a range of assays in vitro which could provide some explanation for the endocrine disrupting properties described in aquatic populations. In terms of oestrogenic activity, triclosan displaced [(3)H]oestradiol from oestrogen receptors (ER) of MCF7 human breast cancer cells and from recombinant human ER alpha/ER beta. Triclosan at 10(-5) m completely inhibited the induction of the oestrogen-responsive ERE-CAT reporter gene in MCF7 cells by 10(-10) m 17beta-oestradiol and the stimulation of growth of MCF7 human breast cancer cells by 10(-10) m 17beta-oestradiol. On its own, 1 microm triclosan increased the growth of MCF7 cells over 21 days. Triclosan also had androgenic activity. It displaced [(3)H]testosterone from binding to the ligand binding domain of the rat androgen receptor (AR). Triclosan was able to inhibit the induction of the androgen-responsive LTR-CAT reporter gene in S115 mouse mammary tumour cells by 10(-9) m testosterone and in T47D human breast cancer cells by 10(-8) m testosterone at concentrations of 10(-7) m and 10(-6) m, respectively. Triclosan at 2 x 10(-5) m antagonized the stimulation of the growth of S115+A mouse mammary tumour cells by 10(-9) m testosterone. The finding that triclosan has oestrogenic and androgenic activity warrants further investigation in relation to both endocrine disruption of aquatic wildlife and any possible impact on human health.
Gee
R H
RH
School of Biological Sciences, The University of Reading, Reading, RG6 6AJ, UK.
Charles
A
A
Taylor
N
N
Darbre
P D
PD
D000728:Androgens / Q000494:pharmacology*; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D001667:Binding, Competitive; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D011944:Receptors, Androgen / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D014260:Triclosan / Q000494:pharmacology*
D000728:Androgens; D000891:Anti-Infective Agents, Local; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004968:Estrogens, Non-Steroidal; D011944:Receptors, Androgen; D014260:Triclosan