Zinc Influences the Efficacy of Betulinic Acid Treatment and Radiotherapy in Breast Cancer Cells

The trace element zinc influences a number of biological reactions, including cell growth, apoptosis, and DNA damage, which affect tumor therapy. The natural compound betulinic acid (BA) and its derivatives are known for their antiviral, antibacterial, and antitumor effects. Previous studies show th...

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Main Authors: Antje Güttler, Elisa Darnstaedt, Danny Knobloch-Sperlich, Marina Petrenko, Jacqueline Kessler, Ivo Grosse, Dirk Vordermark, Matthias Bache
Format: Article
Language:English
Published: MDPI AG 2024-10-01
Series:Antioxidants
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Online Access:https://www.mdpi.com/2076-3921/13/11/1299
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author Antje Güttler
Elisa Darnstaedt
Danny Knobloch-Sperlich
Marina Petrenko
Jacqueline Kessler
Ivo Grosse
Dirk Vordermark
Matthias Bache
author_facet Antje Güttler
Elisa Darnstaedt
Danny Knobloch-Sperlich
Marina Petrenko
Jacqueline Kessler
Ivo Grosse
Dirk Vordermark
Matthias Bache
author_sort Antje Güttler
collection DOAJ
description The trace element zinc influences a number of biological reactions, including cell growth, apoptosis, and DNA damage, which affect tumor therapy. The natural compound betulinic acid (BA) and its derivatives are known for their antiviral, antibacterial, and antitumor effects. Previous studies show that BA and 3-acetyl-28-sulfamoyloxybetulin (CAI3) have high cytotoxicity and induce radiosensitization in breast cancer cells. This study investigates the effects of zinc supplementation on treatment with BA or CAI3 and radiotherapy of breast cancer cell lines MDA-MB-231 and HS578T. Expression analysis shows that BA and CAI3 lead to altered expression of genes involved in zinc metabolism. Zinc supplementation affects cell survival and cell death alone and in combination with BA or CAI3 in both breast cancer cell lines. In MDA-MB-231 cells, zinc excess protects against ROS formation by BA or CAI3 and exhibits radioprotective effects compared to the single agent treatment. In contrast, in HS578T cells, zinc induces ROS formation but does not affect radiosensitivity. The variable effects of zinc on radiosensitivity highlight the importance of individualized treatment approaches. Although zinc has cytotoxic, pro-apoptotic, and anti-clonogenic effects, it seems worthwhile to consider its radioprotective properties when making treatment decisions in the case of adjuvant radiotherapy of breast cancer.
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spelling doaj-art-6115da9bea60468ba8edb2a68bdb68762025-08-20T02:08:12ZengMDPI AGAntioxidants2076-39212024-10-011311129910.3390/antiox13111299Zinc Influences the Efficacy of Betulinic Acid Treatment and Radiotherapy in Breast Cancer CellsAntje Güttler0Elisa Darnstaedt1Danny Knobloch-Sperlich2Marina Petrenko3Jacqueline Kessler4Ivo Grosse5Dirk Vordermark6Matthias Bache7Department of Radiotherapy, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06114 Halle, GermanyDepartment of Radiotherapy, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06114 Halle, GermanyDepartment of Radiotherapy, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06114 Halle, GermanyDepartment of Radiotherapy, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06114 Halle, GermanyDepartment of Radiotherapy, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06114 Halle, GermanyInstitute of Computer Science, Martin Luther University Halle-Wittenberg, Von-Seckendorff-Platz 1, 06120 Halle, GermanyDepartment of Radiotherapy, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06114 Halle, GermanyDepartment of Radiotherapy, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06114 Halle, GermanyThe trace element zinc influences a number of biological reactions, including cell growth, apoptosis, and DNA damage, which affect tumor therapy. The natural compound betulinic acid (BA) and its derivatives are known for their antiviral, antibacterial, and antitumor effects. Previous studies show that BA and 3-acetyl-28-sulfamoyloxybetulin (CAI3) have high cytotoxicity and induce radiosensitization in breast cancer cells. This study investigates the effects of zinc supplementation on treatment with BA or CAI3 and radiotherapy of breast cancer cell lines MDA-MB-231 and HS578T. Expression analysis shows that BA and CAI3 lead to altered expression of genes involved in zinc metabolism. Zinc supplementation affects cell survival and cell death alone and in combination with BA or CAI3 in both breast cancer cell lines. In MDA-MB-231 cells, zinc excess protects against ROS formation by BA or CAI3 and exhibits radioprotective effects compared to the single agent treatment. In contrast, in HS578T cells, zinc induces ROS formation but does not affect radiosensitivity. The variable effects of zinc on radiosensitivity highlight the importance of individualized treatment approaches. Although zinc has cytotoxic, pro-apoptotic, and anti-clonogenic effects, it seems worthwhile to consider its radioprotective properties when making treatment decisions in the case of adjuvant radiotherapy of breast cancer.https://www.mdpi.com/2076-3921/13/11/1299breast cancerbetulinic acidzincROSradiationradiosensitivity
spellingShingle Antje Güttler
Elisa Darnstaedt
Danny Knobloch-Sperlich
Marina Petrenko
Jacqueline Kessler
Ivo Grosse
Dirk Vordermark
Matthias Bache
Zinc Influences the Efficacy of Betulinic Acid Treatment and Radiotherapy in Breast Cancer Cells
Antioxidants
breast cancer
betulinic acid
zinc
ROS
radiation
radiosensitivity
title Zinc Influences the Efficacy of Betulinic Acid Treatment and Radiotherapy in Breast Cancer Cells
title_full Zinc Influences the Efficacy of Betulinic Acid Treatment and Radiotherapy in Breast Cancer Cells
title_fullStr Zinc Influences the Efficacy of Betulinic Acid Treatment and Radiotherapy in Breast Cancer Cells
title_full_unstemmed Zinc Influences the Efficacy of Betulinic Acid Treatment and Radiotherapy in Breast Cancer Cells
title_short Zinc Influences the Efficacy of Betulinic Acid Treatment and Radiotherapy in Breast Cancer Cells
title_sort zinc influences the efficacy of betulinic acid treatment and radiotherapy in breast cancer cells
topic breast cancer
betulinic acid
zinc
ROS
radiation
radiosensitivity
url https://www.mdpi.com/2076-3921/13/11/1299
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