Oxidative damage to hyaluronan-CD44 interactions as an underlying mechanism of action of oxidative stress-inducing cancer therapy
Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved..
Multiple cancer therapies nowadays rely on oxidative stress to damage cancer cells. Here we investigated the biological and molecular effect of oxidative stress on the interaction between CD44 and hyaluronan (HA), as interrupting their binding can hinder cancer progression. Our experiments demonstrated that the oxidation of HA decreased its recognition by CD44, which was further enhanced when both CD44 and HA were oxidized. The reduction of CD44-HA binding negatively affected the proliferative state of cancer cells. Our multi-level atomistic simulations revealed that the binding free energy of HA to CD44 decreased upon oxidation. The effect of HA and CD44 oxidation on CD44-HA binding was similar, but when both HA and CD44 were oxidized, the effect was much larger, in agreement with our experiments. Hence, our experiments and computations support our hypothesis on the role of oxidation in the disturbance of CD44-HA interaction, which can lead to the inhibition of proliferative signaling pathways inside the tumor cell to induce cell death.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:43 |
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| Enthalten in: |
Redox biology - 43(2021) vom: 11. Juli, Seite 101968 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yusupov, Maksudbek [VerfasserIn] |
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| Links: |
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| Themen: |
9004-61-9 |
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| Anmerkungen: |
Date Completed 05.07.2021 Date Revised 31.05.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.redox.2021.101968 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM324490496 |
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| 520 | |a Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a Multiple cancer therapies nowadays rely on oxidative stress to damage cancer cells. Here we investigated the biological and molecular effect of oxidative stress on the interaction between CD44 and hyaluronan (HA), as interrupting their binding can hinder cancer progression. Our experiments demonstrated that the oxidation of HA decreased its recognition by CD44, which was further enhanced when both CD44 and HA were oxidized. The reduction of CD44-HA binding negatively affected the proliferative state of cancer cells. Our multi-level atomistic simulations revealed that the binding free energy of HA to CD44 decreased upon oxidation. The effect of HA and CD44 oxidation on CD44-HA binding was similar, but when both HA and CD44 were oxidized, the effect was much larger, in agreement with our experiments. Hence, our experiments and computations support our hypothesis on the role of oxidation in the disturbance of CD44-HA interaction, which can lead to the inhibition of proliferative signaling pathways inside the tumor cell to induce cell death | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Binding free energy | |
| 650 | 4 | |a Cancer therapies | |
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| 650 | 4 | |a Hyaluronan-CD44 interaction | |
| 650 | 4 | |a Oxidative stress | |
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| 700 | 1 | |a Cordeiro, Rodrigo M |e verfasserin |4 aut | |
| 700 | 1 | |a Verswyvel, Hanne |e verfasserin |4 aut | |
| 700 | 1 | |a Shaw, Priyanka |e verfasserin |4 aut | |
| 700 | 1 | |a Razzokov, Jamoliddin |e verfasserin |4 aut | |
| 700 | 1 | |a Smits, Evelien |e verfasserin |4 aut | |
| 700 | 1 | |a Bogaerts, Annemie |e verfasserin |4 aut | |
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