Regular Article
Differential Membrane Antioxidant Effects of Immediate and Long-Term Estradiol Treatment of MCF-7 Breast Cancer Cells

https://doi.org/10.1006/bbrc.1999.0937Get rights and content

Abstract

Previous studies have documented the direct antioxidant effects of estradiol, and it is tempting to ascribe the antiapoptosis effects of estradiol to its scavenging of reactive oxygen species. However, recent reports have also demonstrated that long-term exposure of MCF-7 human breast cancer cells to estradiol results in estrogen receptor- and estradiol dose-dependent overexpression of the antiapoptosis gene, bcl-2. We have used the pattern of protection of membrane phospholipids from oxidation as a probe to separate these direct and indirect effects of estradiol from one another. Immediate exposure to estradiol non-specifically protects all membrane phospholipids from oxidation by the diazo radical initiator, AMVN. This implies the direct antioxidant activity of estradiol in this system. In contrast, long-term exposure, with associated increased expression of bcl-2, protects only phosphatidylserine, the oxidation of which is a critical component of the final common pathway for apoptosis. This bcl-2-mediated indirect effect of estradiol is accompanied by prevention of apoptosis in MCF-7 cells.

References (16)

  • K.K. Koh et al.

    Am. J. Cardiol.

    (1997)
  • P.S. Green et al.

    Neuroscience

    (1998)
  • H. Albrecht et al.

    FEBS Lett.

    (1994)
  • Y.Y. Tyurina et al.

    Arch. Biochem. Biophys.

    (1997)
  • V.B. Ritov et al.

    Biochim. Biophys. Acta

    (1996)
  • J. Cai et al.

    Biochim. Biophys. Acta

    (1998)
  • J. Cai et al.

    J. Biol. Chem.

    (1998)
There are more references available in the full text version of this article.

Cited by (14)

  • Estradiol protects against hippocampal damage and impairments in fear conditioning resulting from transient global ischemia in mice

    2012, Brain Research
    Citation Excerpt :

    In contrast, the ERβ agonist diarylpropionitrile (DPN), but not the ERα agonist PPT, protects against 2-VO-induced damage in mice (Carswell et al., 2004). Estradiol, ERα-specific agonists, and ERβ-specific agonists have all been shown to up-regulate the expression of the anti-apoptotic marker Bcl-2 resulting in improved cell survival (Alkayed et al., 2001; Dubal et al., 1999; Schor et al., 1999; Zhao et al., 2004). While pharmacologically targeting specific estrogen receptors is a valuable strategy to employ toward understanding the mechanisms through which estradiol exerts its protective effects, use of genetically-modified mice provides a particularly powerful, complementary approach.

  • 17-Beta-estradiol protects the liver against warm ischemia/reperfusion injury and is associated with increased serum nitric oxide and decreased tumor necrosis factor-alpha

    2002, Surgery
    Citation Excerpt :

    Estrogen administration has been shown to reduce ICAM 1 and major histocompatibility class II expression on endothelial cells; therefore, lower expression of adhesion molecules and other markers of endothelial cell activation can be directly mediated by estrogens. The cytoprotective effects of estrogens have been shown to be receptor dependent and independent.27,28 Arnal et al27 demonstrated that the antioxidant effects of estrogens are receptor independent, and that probably explains the fact that some of the hepatoprotective effects of estrogens in our study were not completely reverted after the administration of the high affinity receptor blocker ICI 182,780.

View all citing articles on Scopus
1

On leave from the Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Science, St. Petersburg, 194223, Russia.

View full text