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  • Lower concentrations of phthalates induce proliferation in human breast cancer cells.

Lower concentrations of phthalates induce proliferation in human breast cancer cells.

Climacteric : the journal of the International Menopause Society (2013-11-16)
F-P Chen, M-H Chien
ABSTRACT

To explore the effect and pathway of phthalates on the growth of MCF-7 breast cancer cells. MCF-7 cells were treated with benzyl butyl phthalate (BBP), di-n-butyl phthalate (DBP), and di-2-ethylhexyl phthalate (DEHP) (10(-10)-10(-4) mol/l). After incubation for 24, 48, 72, and 92 h, the cells were harvested and extracted for 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The proteins involving proliferative and apoptotic pathways were evaluated by Western blot analysis. MTT assay revealed cell toxicity at more than 10(-5) mol/l for DEHP and at 10(-4) mol/l for both BBP and DBP in MCF-7 cells. Cell proliferation was significantly increased at 10(-8)-10(-5) mol/l of BBP and DBP, and at 10(-8)-10(-6) mol/l of DEHP treatment. Proliferating cell nuclear antigen (PCNA) was substantially increased in cultures with DEHP (10(-8)-10(-6) mol/l), BBP (10(-8)-10(-5) mol/l), and DBP (10(-7)-10(-5) mol/l). Obvious increases in PI3K, p-AKT, and PCNA were noted in cultures with 17β-estradiol, BBP, DBP, and DEHP. Estrogen receptor α expression was also notably increased in treatment with estradiol, BBP, DBP, and DEHP. The present study demonstrates that, even at a very low concentration, BBP, DBP, and DEHP were not only still capable of inducing a proliferative effect through the PI3K/AKT signaling pathway but also displaying estrogenic activity. Therefore, the current reference doses for phthalates defined by governments should be further evaluated.

MATERIALS
Product Number
Brand
Product Description

Supelco
Bis(2-ethylhexyl) phthalate, PESTANAL®, analytical standard
Supelco
Bis(2-ethylhexyl) phthalate, Selectophore
Supelco
Bis(2-ethylhexyl) phthalate, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
Plastic additive 01, European Pharmacopoeia (EP) Reference Standard