title: Effect of tamoxifen and fulvestrant long-term treatments on ROS production and (pro/anti)-oxidant enzymes mRNA levels in a MCF-7-derived breast cancer cell line.
abstract: BACKGROUND
  Reactive oxygen species (ROS) are key players in the apoptotic effects induced by short-term tamoxifen treatment of breast cancer cells, but also in acquired resistance following long-term treatment. Whereas the use of the selective estrogen receptor down-regulator fulvestrant is promising, especially in patients who develop tamoxifen resistance, only few studies addressed its implication in the modulation of cellular redox status.
  
  
  METHODS
  The regulation of (pro/anti)-oxidant players were first investigated at the mRNA level in a MCF-7-derived cell line after short-term (24 h) estradiol treatment. Long-term anti-estrogen treated MCF-7 derived cell lines were also developed: 3 months of 4-hydroxytamoxifen alone (MCF7L-OHTLT) or followed by 3 months of fulvestrant (MCF7L-ICILT). Growth properties, hormone sensitivity, receptor content, ROS production and relative mRNA expression of pro or antioxidant enzymes were evaluated in these long-term treated cell lines.
  
  
  RESULTS
  Short-term estradiol treatment showed a hormone sensitivity of Nox2, GPx1, GPx2 and SOD1 mRNA levels. The long-term fulvestrant treatment (3 months) of MCF7L-OHTLT led to a reduced level of ROS production accompanied with a drastic drop of the accessory protein p22(phox) mRNA. This ROS reduction, although not clearly related to antioxidant enzymes level, seems to be involved in fulvestrant sensitivity of long-term anti-estrogen treated cells, as suggested by the effects of antiradical tempol treatment.
  
  
  CONCLUSIONS
  When compared to long-term 4-hydroxytamoxifen-treated breast cancer cells, addition of fulvestrant treatment was able to diminish ROS production and p22(phox) mRNA level, and made cells more sensitive to growth inhibition induced by tempol. These effects may be a valuable asset of the fulvestrant treatment.
authors.affiliation: PhyMedExp, UMR CNRS 9214, Inserm U1046, Université de Montpellier, 34295, Montpellier Cedex 5, France. eric.badia@univ-montp1.fr.|INSERM, U1046, IURC, 641 Avenue du Doyen Gaston Giraud, 34093, Montpellier, France. eric.badia@univ-montp1.fr.
authors.forename: Eric
authors.identifier: http://orcid.org/0000-0001-8162-5392
authors.initials: E
authors.lastname: Badia
authors.affiliation: PhyMedExp, UMR CNRS 9214, Inserm U1046, Université de Montpellier, 34295, Montpellier Cedex 5, France.|INSERM, U1046, IURC, 641 Avenue du Doyen Gaston Giraud, 34093, Montpellier, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Morena
authors.affiliation: PhyMedExp, UMR CNRS 9214, Inserm U1046, Université de Montpellier, 34295, Montpellier Cedex 5, France.|INSERM, U1046, IURC, 641 Avenue du Doyen Gaston Giraud, 34093, Montpellier, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Lauret
authors.affiliation: IRCM, Institut de Recherche en Cancérologie de Montpellier, 34298, Montpellier, France.|INSERM, U1194, 34298, Montpellier, France.|ICM, Institut régional du Cancer de Montpellier, 34298, Montpellier, France.
authors.forename: Abdelhay
authors.initials: A
authors.lastname: Boulahtouf
authors.affiliation: CHU de Montpellier Arnaud de Villeneuve, 371, Avenue Doyen Gaston Giraud, 34295, Montpellier Cedex 5, France.|Université de Montpellier, 34090, Montpellier, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Boulle
authors.affiliation: IRCM, Institut de Recherche en Cancérologie de Montpellier, 34298, Montpellier, France.|INSERM, U1194, 34298, Montpellier, France.|ICM, Institut régional du Cancer de Montpellier, 34298, Montpellier, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Cavaillès
authors.affiliation: IRCM, Institut de Recherche en Cancérologie de Montpellier, 34298, Montpellier, France.|INSERM, U1194, 34298, Montpellier, France.|ICM, Institut régional du Cancer de Montpellier, 34298, Montpellier, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Balaguer
authors.affiliation: PhyMedExp, UMR CNRS 9214, Inserm U1046, Université de Montpellier, 34295, Montpellier Cedex 5, France.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Cristol
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism; D045744:Cell Line, Tumor; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004798:Enzymes / Q000235:genetics* / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000077267:Fulvestrant; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000072019:Kelch-Like ECH-Associated Protein 1 / Q000235:genetics; D061986:MCF-7 Cells / Q000187:drug effects / Q000378:metabolism; D019255:NADPH Oxidases / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013113:Spin Labels; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D000975:Antioxidants; D003497:Cyclic N-Oxides; D004798:Enzymes; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D017382:Reactive Oxygen Species; D013113:Spin Labels; D013629:Tamoxifen; C016601:afimoxifene; D000077267:Fulvestrant; D004958:Estradiol; D019255:NADPH Oxidases; C086986:CYBA protein, human; C001803:tempol
keywords: Anti-estrogens; Breast; Cancer; MCF-7; Oxidative stress