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Lipid peroxidation increases hydrogen peroxide permeability leading to cell death in cancer cell lines that lack mtDNA
4‐Hydroxynonenal (HNE) is an important product of plasma membrane lipid peroxidation, which is a cause of cell and tissue injury. Mitochondrial DNA (mtDNA)‐depleted ρ(0) cells were established using human cervical cancer and oral squamous cell carcinoma cell lines. We investigated the effect of reac...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726706/ https://www.ncbi.nlm.nih.gov/pubmed/31314163 http://dx.doi.org/10.1111/cas.14132 |
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author | Tomita, Kazuo Takashi, Yuko Ouchi, Yuya Kuwahara, Yoshikazu Igarashi, Kento Nagasawa, Taisuke Nabika, Hideki Kurimasa, Akihiro Fukumoto, Manabu Nishitani, Yoshihiro Sato, Tomoaki |
author_facet | Tomita, Kazuo Takashi, Yuko Ouchi, Yuya Kuwahara, Yoshikazu Igarashi, Kento Nagasawa, Taisuke Nabika, Hideki Kurimasa, Akihiro Fukumoto, Manabu Nishitani, Yoshihiro Sato, Tomoaki |
author_sort | Tomita, Kazuo |
collection | PubMed |
description | 4‐Hydroxynonenal (HNE) is an important product of plasma membrane lipid peroxidation, which is a cause of cell and tissue injury. Mitochondrial DNA (mtDNA)‐depleted ρ(0) cells were established using human cervical cancer and oral squamous cell carcinoma cell lines. We investigated the effect of reactive oxygen species in ρ(0) cells, especially the mechanism of hydrogen peroxide (H(2)O(2))‐mediated cell death. These cell were subjected to high oxidative stress and, compared with their parental cells, showed greater sensitivity to H(2)O(2) and high lipid peroxidation. Upregulation of HNE in the plasma membrane was observed prior to the increase in intracellular H(2)O(2). The amount of oxidized lipid present changed H(2)O(2) permeability and administration of oxidized lipid led to further cell death after treatment with H(2)O(2). Expression levels of lipoxygenase ALOX genes (ie ALOX5, ALOX12, and ALOX15) were upregulated in ρ(0) cells, as were expression levels of ALOX12 and ALOX15 proteins. ALOX5 protein was mainly distributed in the nucleus, while ALOX12 and ALOX15 proteins were distributed in the nucleus and the cytoplasm. Although expression of COX2 gene was upregulated, its protein expression did not increase. ALOX (especially ALOX15) may be involved in the sensitivity of cancer cells to treatment. These data offer promise for the development of novel anticancer agents by altering the oxidation state of the plasma membrane. Our results showed that lipid peroxidation status is important for H(2)O(2) sensitivity and that ALOX15 is involved in lipid peroxidation status. |
format | Online Article Text |
id | pubmed-6726706 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-67267062019-09-10 Lipid peroxidation increases hydrogen peroxide permeability leading to cell death in cancer cell lines that lack mtDNA Tomita, Kazuo Takashi, Yuko Ouchi, Yuya Kuwahara, Yoshikazu Igarashi, Kento Nagasawa, Taisuke Nabika, Hideki Kurimasa, Akihiro Fukumoto, Manabu Nishitani, Yoshihiro Sato, Tomoaki Cancer Sci Original Articles 4‐Hydroxynonenal (HNE) is an important product of plasma membrane lipid peroxidation, which is a cause of cell and tissue injury. Mitochondrial DNA (mtDNA)‐depleted ρ(0) cells were established using human cervical cancer and oral squamous cell carcinoma cell lines. We investigated the effect of reactive oxygen species in ρ(0) cells, especially the mechanism of hydrogen peroxide (H(2)O(2))‐mediated cell death. These cell were subjected to high oxidative stress and, compared with their parental cells, showed greater sensitivity to H(2)O(2) and high lipid peroxidation. Upregulation of HNE in the plasma membrane was observed prior to the increase in intracellular H(2)O(2). The amount of oxidized lipid present changed H(2)O(2) permeability and administration of oxidized lipid led to further cell death after treatment with H(2)O(2). Expression levels of lipoxygenase ALOX genes (ie ALOX5, ALOX12, and ALOX15) were upregulated in ρ(0) cells, as were expression levels of ALOX12 and ALOX15 proteins. ALOX5 protein was mainly distributed in the nucleus, while ALOX12 and ALOX15 proteins were distributed in the nucleus and the cytoplasm. Although expression of COX2 gene was upregulated, its protein expression did not increase. ALOX (especially ALOX15) may be involved in the sensitivity of cancer cells to treatment. These data offer promise for the development of novel anticancer agents by altering the oxidation state of the plasma membrane. Our results showed that lipid peroxidation status is important for H(2)O(2) sensitivity and that ALOX15 is involved in lipid peroxidation status. John Wiley and Sons Inc. 2019-07-27 2019-09 /pmc/articles/PMC6726706/ /pubmed/31314163 http://dx.doi.org/10.1111/cas.14132 Text en © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Tomita, Kazuo Takashi, Yuko Ouchi, Yuya Kuwahara, Yoshikazu Igarashi, Kento Nagasawa, Taisuke Nabika, Hideki Kurimasa, Akihiro Fukumoto, Manabu Nishitani, Yoshihiro Sato, Tomoaki Lipid peroxidation increases hydrogen peroxide permeability leading to cell death in cancer cell lines that lack mtDNA |
title | Lipid peroxidation increases hydrogen peroxide permeability leading to cell death in cancer cell lines that lack mtDNA |
title_full | Lipid peroxidation increases hydrogen peroxide permeability leading to cell death in cancer cell lines that lack mtDNA |
title_fullStr | Lipid peroxidation increases hydrogen peroxide permeability leading to cell death in cancer cell lines that lack mtDNA |
title_full_unstemmed | Lipid peroxidation increases hydrogen peroxide permeability leading to cell death in cancer cell lines that lack mtDNA |
title_short | Lipid peroxidation increases hydrogen peroxide permeability leading to cell death in cancer cell lines that lack mtDNA |
title_sort | lipid peroxidation increases hydrogen peroxide permeability leading to cell death in cancer cell lines that lack mtdna |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726706/ https://www.ncbi.nlm.nih.gov/pubmed/31314163 http://dx.doi.org/10.1111/cas.14132 |
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