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Carcinogenesis, Vol. 20, No. 11, 2057-2061, November 1999
© 1999 Oxford University Press

Cancer Biology

Effects of environmental estrogens on tumor necrosis factor {alpha}-mediated apoptosis in MCF-7 cells

Matthew E Burow1,2,3,4, Yan Tang2,4, Bridgette M. Collins-Burow11,3, Stanislaw Krajewski6, John C. Reed6, John A. McLachlan1,2,3,5 and Barbara S Beckman1,2,3,4,7

1 Molecular and Cellular Biology Program,
2 Department of Pharmacology,
3 Tulane-Xavier Center for Bioenvironmental Research,
4 Tulane Cancer Center and
5 Department of Environmental Health Sciences, Tulane University School of Medicine, New Orleans, LA 70112 and
6 The Burnham Institute, La Jolla, CA 92037-1062, USA

Environmental estrogens represent a class of compounds which have been shown to mimic the effects or activity of the naturally occurring ovarian hormone 17ß-estradiol. Given the role of 17ß-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 17ß-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, 17ß-estradiol, and function to suppress apoptosis in ER-responsive cells.

Abbreviations: alachlor, 2-chloro-N-(2,6-diethylphenyl)-N-(methoxymethyl)acetamide; o,p' DDT, 1,1,1-trichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl) ethane; DMEM, Dulbecco's modified Eagle's medium; endosulfan II (3{alpha},5aß,6ß,9ß,9aß)-6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepin 3-oxide: ER, estrogen receptor; ERE, estrogen response element; FBS, fetal bovine serum; TNF, tumor necrosis factor {alpha}.

7 To whom correspondence should be addressed at: Tulane University Medical Center, Department of Pharmacology SL-83, 1430 Tulane Avenue, New Orleans, LA 70112, USA Email: bbeckman{at}tmcpop.tmc.tulane.edu


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