Differential response to α-oxoaldehydes in tamoxifen resistant MCF-7 breast cancer cells.
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 li...
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doaj-ed2045353b0b4f2a9dcd740c593f972e2021-06-19T04:58:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e10147310.1371/journal.pone.0101473Differential response to α-oxoaldehydes in tamoxifen resistant MCF-7 breast cancer cells.Norbert NassHans-Jürgen BrömmeRoland HartigSevil KorkmazSaadettin SelFrank HircheAoife WardAndreas SimmStefan WiemannAnne E LykkesfeldtAlbert RoessnerThomas KalinskiTamoxifen 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24983248/pdf/?tool=EBI |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Norbert Nass Hans-Jürgen Brömme Roland Hartig Sevil Korkmaz Saadettin Sel Frank Hirche Aoife Ward Andreas Simm Stefan Wiemann Anne E Lykkesfeldt Albert Roessner Thomas Kalinski |
spellingShingle |
Norbert Nass Hans-Jürgen Brömme Roland Hartig Sevil Korkmaz Saadettin Sel Frank Hirche Aoife Ward Andreas Simm Stefan Wiemann Anne E Lykkesfeldt Albert Roessner Thomas Kalinski Differential response to α-oxoaldehydes in tamoxifen resistant MCF-7 breast cancer cells. PLoS ONE |
author_facet |
Norbert Nass Hans-Jürgen Brömme Roland Hartig Sevil Korkmaz Saadettin Sel Frank Hirche Aoife Ward Andreas Simm Stefan Wiemann Anne E Lykkesfeldt Albert Roessner Thomas Kalinski |
author_sort |
Norbert Nass |
title |
Differential response to α-oxoaldehydes in tamoxifen resistant MCF-7 breast cancer cells. |
title_short |
Differential response to α-oxoaldehydes in tamoxifen resistant MCF-7 breast cancer cells. |
title_full |
Differential response to α-oxoaldehydes in tamoxifen resistant MCF-7 breast cancer cells. |
title_fullStr |
Differential response to α-oxoaldehydes in tamoxifen resistant MCF-7 breast cancer cells. |
title_full_unstemmed |
Differential response to α-oxoaldehydes in tamoxifen resistant MCF-7 breast cancer cells. |
title_sort |
differential response to α-oxoaldehydes in tamoxifen resistant mcf-7 breast cancer cells. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
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. |
url |
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24983248/pdf/?tool=EBI |
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