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OxLDL as an Inducer of a Metabolic Shift in Cancer Cells

Recent evidence established a link between disturbed lipid metabolism and increased risk for cancer. One of the most prominent features related to disturbed lipid metabolism is an increased production of oxidized low-density-lipoproteins (oxLDL), which results from elevated oxidative stress. OxLDL i...

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Autores principales: Bitorina, Albert V., Oligschlaeger, Yvonne, Ding, Lingling, Yadati, Tulasi, Westheim, Annemarie, Houben, Tom, Vaes, Rianne D.W., Olde Damink, Steven W.M., Theys, Jan, Shiri-Sverdlov, Ronit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408103/
https://www.ncbi.nlm.nih.gov/pubmed/34475995
http://dx.doi.org/10.7150/jca.56307
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author Bitorina, Albert V.
Oligschlaeger, Yvonne
Ding, Lingling
Yadati, Tulasi
Westheim, Annemarie
Houben, Tom
Vaes, Rianne D.W.
Olde Damink, Steven W.M.
Theys, Jan
Shiri-Sverdlov, Ronit
author_facet Bitorina, Albert V.
Oligschlaeger, Yvonne
Ding, Lingling
Yadati, Tulasi
Westheim, Annemarie
Houben, Tom
Vaes, Rianne D.W.
Olde Damink, Steven W.M.
Theys, Jan
Shiri-Sverdlov, Ronit
author_sort Bitorina, Albert V.
collection PubMed
description Recent evidence established a link between disturbed lipid metabolism and increased risk for cancer. One of the most prominent features related to disturbed lipid metabolism is an increased production of oxidized low-density-lipoproteins (oxLDL), which results from elevated oxidative stress. OxLDL is known to have detrimental effects on healthy cells and plays a primary role in diseases related to the metabolic syndrome. Nevertheless, so far, the exact role of oxLDL in cancer cell metabolism is not yet known. To examine changes in metabolic profile induced by oxLDL, pancreatic KLM-1 cells were treated with oxLDL in a concentration- (25 or 50 µg/ml) and/or time-dependent (4 hr or 8 hr) manner and the impact of oxLDL on oxygen consumption rates (OCR) as well as extracellular acidification rates (ECAR) was analyzed using Seahorse technology. Subsequently, to establish the link between oxLDL and glycolysis, stabilization of the master regulator hypoxia-inducible factor 1-alpha (HIF-1α) was measured by means of Western blot. Furthermore, autophagic responses were assessed by measuring protein levels of the autophagosomal marker LC3B-II. Finally, the therapeutic potential of natural anti-oxLDL IgM antibodies in reversing these effects was tested. Incubation of KLM-1 cells with oxLDL shifted the energy balance towards a more glycolytic phenotype, which is an important hallmark of cancer cells. These data were supported by measurement of increased oxLDL-mediated HIF-1α stabilization. In line, oxLDL incubation also increased the levels of LC3B-II, suggesting an elevated autophagic response. Importantly, antibodies against oxLDL were able to reverse these oxLDL-mediated metabolic effects. Our data provides a novel proof-of-concept that oxLDL induces a shift in energy balance. These data not only support a role for oxLDL in the progression of cancer but also suggest the possibility of targeting oxLDL as a therapeutic option in cancer.
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spelling pubmed-84081032021-09-01 OxLDL as an Inducer of a Metabolic Shift in Cancer Cells Bitorina, Albert V. Oligschlaeger, Yvonne Ding, Lingling Yadati, Tulasi Westheim, Annemarie Houben, Tom Vaes, Rianne D.W. Olde Damink, Steven W.M. Theys, Jan Shiri-Sverdlov, Ronit J Cancer Research Paper Recent evidence established a link between disturbed lipid metabolism and increased risk for cancer. One of the most prominent features related to disturbed lipid metabolism is an increased production of oxidized low-density-lipoproteins (oxLDL), which results from elevated oxidative stress. OxLDL is known to have detrimental effects on healthy cells and plays a primary role in diseases related to the metabolic syndrome. Nevertheless, so far, the exact role of oxLDL in cancer cell metabolism is not yet known. To examine changes in metabolic profile induced by oxLDL, pancreatic KLM-1 cells were treated with oxLDL in a concentration- (25 or 50 µg/ml) and/or time-dependent (4 hr or 8 hr) manner and the impact of oxLDL on oxygen consumption rates (OCR) as well as extracellular acidification rates (ECAR) was analyzed using Seahorse technology. Subsequently, to establish the link between oxLDL and glycolysis, stabilization of the master regulator hypoxia-inducible factor 1-alpha (HIF-1α) was measured by means of Western blot. Furthermore, autophagic responses were assessed by measuring protein levels of the autophagosomal marker LC3B-II. Finally, the therapeutic potential of natural anti-oxLDL IgM antibodies in reversing these effects was tested. Incubation of KLM-1 cells with oxLDL shifted the energy balance towards a more glycolytic phenotype, which is an important hallmark of cancer cells. These data were supported by measurement of increased oxLDL-mediated HIF-1α stabilization. In line, oxLDL incubation also increased the levels of LC3B-II, suggesting an elevated autophagic response. Importantly, antibodies against oxLDL were able to reverse these oxLDL-mediated metabolic effects. Our data provides a novel proof-of-concept that oxLDL induces a shift in energy balance. These data not only support a role for oxLDL in the progression of cancer but also suggest the possibility of targeting oxLDL as a therapeutic option in cancer. Ivyspring International Publisher 2021-08-03 /pmc/articles/PMC8408103/ /pubmed/34475995 http://dx.doi.org/10.7150/jca.56307 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Bitorina, Albert V.
Oligschlaeger, Yvonne
Ding, Lingling
Yadati, Tulasi
Westheim, Annemarie
Houben, Tom
Vaes, Rianne D.W.
Olde Damink, Steven W.M.
Theys, Jan
Shiri-Sverdlov, Ronit
OxLDL as an Inducer of a Metabolic Shift in Cancer Cells
title OxLDL as an Inducer of a Metabolic Shift in Cancer Cells
title_full OxLDL as an Inducer of a Metabolic Shift in Cancer Cells
title_fullStr OxLDL as an Inducer of a Metabolic Shift in Cancer Cells
title_full_unstemmed OxLDL as an Inducer of a Metabolic Shift in Cancer Cells
title_short OxLDL as an Inducer of a Metabolic Shift in Cancer Cells
title_sort oxldl as an inducer of a metabolic shift in cancer cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408103/
https://www.ncbi.nlm.nih.gov/pubmed/34475995
http://dx.doi.org/10.7150/jca.56307
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