TY - JOUR
T1 - Lower concentrations of phthalates induce proliferation in human breast cancer cells
AU - Chen, F. P.
AU - Chien, M. H.
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
KW - Butyl Benzyl Phthalate
KW - Di-2-Ethylhexyl PHTHALATE
KW - Di-N-Butyl Phthalate
KW - MCF-7 BREAST CANCER CELLS
KW - PI3K/AKT SIGNALING PATHWAY
UR - http://www.scopus.com/inward/record.url?scp=84904345331&partnerID=8YFLogxK
U2 - 10.3109/13697137.2013.865720
DO - 10.3109/13697137.2013.865720
M3 - 文章
C2 - 24228746
AN - SCOPUS:84904345331
SN - 1369-7137
VL - 17
SP - 377
EP - 384
JO - Climacteric
JF - Climacteric
IS - 4
ER -
