Effects of environmental estrogens on tumor necrosis factor alpha-mediated apoptosis in MCF-7 cells.
Environmental estrogens represent a class of compounds which have been shown to mimic the effects or activity of the naturally occurring ovarian hormone 17beta-estradiol. Given the role of 17beta-estradiol in cell survival in a number of systems, we wished to determine if environmental estrogens protect MCF-7 cells from apoptosis. Here we demonstrate that the organochlorine pesticides o, p' DDT and alachlor, like 17beta-estradiol, have the ability to suppress tumor necrosis factor alpha (TNF)-induced apoptosis in estrogen receptor (ER)-positive MCF-7 breast carcinoma cells. These compounds, however, did not affect TNF-induced apoptosis of the ER-negative MDA-MB-231 cell line. The ability of these compounds to suppress apoptosis in MCF-7 cells was correlated with an ER-dependent increase in Bcl-2 expression. Taken together these results demonstrate that estrogenic organochlorine pesticides like o, p' DDT and alachlor may partially mimic the primary endogenous estrogen, 17beta-estradiol, and function to suppress apoptosis in ER-responsive cells.
Burow
M E
ME
Department of Pharmacology, Tulane-Xavier Center for Bioenvironmental Research, Tulane Cancer Center and Department of Environmental Health Sciences, Tulane University School of Medicine, New Orleans, LA70112, USA.
Tang
Y
Y
Collins-Burow
B M
BM
Krajewski
S
S
Reed
J C
JC
McLachlan
J A
JA
Beckman
B S
BS
D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D006801:Humans; D011960:Receptors, Estrogen / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015262:Xenobiotics / Q000494:pharmacology
D004968:Estrogens, Non-Steroidal; D011960:Receptors, Estrogen; D014409:Tumor Necrosis Factor-alpha; D015262:Xenobiotics