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Climacteric. 2014 Aug;17(4):377-84. doi: 10.3109/13697137.2013.865720. Epub 2013 Dec 27.

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

Author information

1
Department of Obstetrics and Gynecology, Keelung Chang Gung Memorial Hospital, Keelung and Chang Gung University , Taiwan.

Abstract

OBJECTIVE:

To explore the effect and pathway of phthalates on the growth of MCF-7 breast cancer cells.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

BUTYL BENZYL PHTHALATE; DI-2-ETHYLHEXYL PHTHALATE; DI-n-BUTYL PHTHALATE; MCF-7 BREAST CANCER CELLS; PI3K/AKT SIGNALING PATHWAY

PMID:
24228746
DOI:
10.3109/13697137.2013.865720
[Indexed for MEDLINE]

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