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PLoS One. 2014 Jul 1;9(7):e101473. doi: 10.1371/journal.pone.0101473. eCollection 2014.

Differential response to α-oxoaldehydes in tamoxifen resistant MCF-7 breast cancer cells.

Author information

1
Department of Pathology, Otto von Guericke University Magdeburg, Magdeburg, Germany.
2
Martin-Luther-University Halle-Wittenberg, Centre for Basic Medical Research (ZMG), Halle, Germany.
3
Otto-von-Guericke-University Medical Faculty, Multidimensional Microscopy and Cellular Diagnostics, Magdeburg, Germany.
4
Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany.
5
Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany.
6
Martin-Luther-University Halle-Wittenberg, Institute of Agricultural and Nutritional Sciences, Halle/Saale, Germany.
7
German Cancer Research Center DKFZ, Division of Molecular Genome Analysis, Heidelberg, Germany.
8
Danish Cancer Society Research Center, Breast Cancer Group, Cell Death and Metabolism, Copenhagen, Denmark.

Erratum in

  • PLoS One. 2014;9(7):e104322.

Abstract

Tamoxifen is the standard adjuvant endocrine therapy for estrogen-receptor positive premenopausal breast cancer patients. However, tamoxifen resistance is frequently observed under therapy. A tamoxifen resistant cell line has been generated from the estrogen receptor positive mamma carcinoma cell line MCF-7 and was analyzed for putative differences in the aldehyde defence system and accumulation of advanced glycation end products (AGE). In comparison to wt MCF-7 cells, these tamoxifen resistant cells were more sensitive to the dicarbonyl compounds glyoxal and methylglyoxal and displayed increased caspase activity, p38-MAPK- and IκBα-phosphorylation. However, mRNA accumulation of the aldehyde- and AGE-defence enzymes glyoxalase-1 and -2 (GLO1, GLO2) as well as fructosamine-3-kinase (FN3K) was not significantly altered. Tamoxifen resistant cells contained less free sulfhydryl-groups (glutathione) suggesting that the increased sensitivity towards the dicarbonyls was due to a higher sensitivity towards reactive oxygen species which are associated with dicarbonyl stress. To further analyse, if these data are of more general importance, key experiments were replicated with tamoxifen resistant MCF-7 cell lines from two independent sources. These cell lines were also more sensitive to aldehydes, especially glyoxal, but were different in their cellular signalling responses to the aldehydes. In conclusion, glyoxalases and other aldehyde defence enzymes might represent a promising target for the therapy of tamoxifen resistant breast cancers.

PMID:
24983248
PMCID:
PMC4077828
DOI:
10.1371/journal.pone.0101473
[Indexed for MEDLINE]
Free PMC Article

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