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Quercetin-Induced Glutathione Depletion Sensitizes Colorectal Cancer Cells to Oxaliplatin

Quercetin is an antioxidant phytochemical which belongs to the natural flavonoids group. Recently, the compound has been reported to inhibit glutathione reductase responsible for replenishing reduced forms of glutathione and thus leads to glutathione depletion, triggering cell death. In this study,...

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Autores principales: Lee, Jinkyung, Jang, Chan Ho, Kim, Yoonsu, Oh, Jisun, Kim, Jong-Sang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138196/
https://www.ncbi.nlm.nih.gov/pubmed/37107528
http://dx.doi.org/10.3390/foods12081733
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author Lee, Jinkyung
Jang, Chan Ho
Kim, Yoonsu
Oh, Jisun
Kim, Jong-Sang
author_facet Lee, Jinkyung
Jang, Chan Ho
Kim, Yoonsu
Oh, Jisun
Kim, Jong-Sang
author_sort Lee, Jinkyung
collection PubMed
description Quercetin is an antioxidant phytochemical which belongs to the natural flavonoids group. Recently, the compound has been reported to inhibit glutathione reductase responsible for replenishing reduced forms of glutathione and thus leads to glutathione depletion, triggering cell death. In this study, we examined if quercetin sensitizes tumors to oxaliplatin by inhibiting glutathione reductase activity in human colorectal cancer cells, and thereby facilitates apoptotic cell death. A combined treatment with quercetin and oxaliplatin was found to synergistically inhibit glutathione reductase activity, lower intracellular glutathione level, increase reactive oxygen species production, and reduce cell viability, compared to treatment with oxaliplatin alone in human colorectal HCT116 cancer cells. Furthermore, the incorporation of sulforaphane, recognized for its ability to scavenge glutathione, in combination with quercetin and oxaliplatin, substantially suppressed tumor growth in an HCT116 xenograft mouse model. These findings suggest that the depletion of intracellular glutathione by quercetin and sulforaphane could strengthen the anti-cancer efficacy of oxaliplatin.
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spelling pubmed-101381962023-04-28 Quercetin-Induced Glutathione Depletion Sensitizes Colorectal Cancer Cells to Oxaliplatin Lee, Jinkyung Jang, Chan Ho Kim, Yoonsu Oh, Jisun Kim, Jong-Sang Foods Article Quercetin is an antioxidant phytochemical which belongs to the natural flavonoids group. Recently, the compound has been reported to inhibit glutathione reductase responsible for replenishing reduced forms of glutathione and thus leads to glutathione depletion, triggering cell death. In this study, we examined if quercetin sensitizes tumors to oxaliplatin by inhibiting glutathione reductase activity in human colorectal cancer cells, and thereby facilitates apoptotic cell death. A combined treatment with quercetin and oxaliplatin was found to synergistically inhibit glutathione reductase activity, lower intracellular glutathione level, increase reactive oxygen species production, and reduce cell viability, compared to treatment with oxaliplatin alone in human colorectal HCT116 cancer cells. Furthermore, the incorporation of sulforaphane, recognized for its ability to scavenge glutathione, in combination with quercetin and oxaliplatin, substantially suppressed tumor growth in an HCT116 xenograft mouse model. These findings suggest that the depletion of intracellular glutathione by quercetin and sulforaphane could strengthen the anti-cancer efficacy of oxaliplatin. MDPI 2023-04-21 /pmc/articles/PMC10138196/ /pubmed/37107528 http://dx.doi.org/10.3390/foods12081733 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Jinkyung
Jang, Chan Ho
Kim, Yoonsu
Oh, Jisun
Kim, Jong-Sang
Quercetin-Induced Glutathione Depletion Sensitizes Colorectal Cancer Cells to Oxaliplatin
title Quercetin-Induced Glutathione Depletion Sensitizes Colorectal Cancer Cells to Oxaliplatin
title_full Quercetin-Induced Glutathione Depletion Sensitizes Colorectal Cancer Cells to Oxaliplatin
title_fullStr Quercetin-Induced Glutathione Depletion Sensitizes Colorectal Cancer Cells to Oxaliplatin
title_full_unstemmed Quercetin-Induced Glutathione Depletion Sensitizes Colorectal Cancer Cells to Oxaliplatin
title_short Quercetin-Induced Glutathione Depletion Sensitizes Colorectal Cancer Cells to Oxaliplatin
title_sort quercetin-induced glutathione depletion sensitizes colorectal cancer cells to oxaliplatin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138196/
https://www.ncbi.nlm.nih.gov/pubmed/37107528
http://dx.doi.org/10.3390/foods12081733
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