Thermal Proteome Profiling Reveals Insight to Antiproliferative and Pro-Apoptotic Effects of Lagunamide A in the Modulation of DNA Damage Repair

Yudong Hu; Dietrich Mostert; Christina Orgler; Oliver Andler; Hans Zischka; Uli Kazmaier; Angelika M. Vollmar; Simone Braig; Stephan A. Sieber; Stefan Zahler

doi:10.1002/cbic.202400024

Thermal Proteome Profiling Reveals Insight to Antiproliferative and Pro-Apoptotic Effects of Lagunamide A in the Modulation of DNA Damage Repair

Yudong Hu, Dietrich Mostert, Christina Orgler, Oliver Andler, Hans Zischka, Uli Kazmaier, Angelika M. Vollmar, Simone Braig, Stephan A. Sieber, Stefan Zahler

Chair of Organic Chemistry II

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Lagunamide A is a biologically active natural product with a yet unidentified molecular mode of action. Cellular studies revealed that lagunamide A is a potent inhibitor of cancer cell proliferation, promotes apoptosis and causes mitochondrial dysfunction. To decipher the cellular mechanism responsible for these effects, we utilized thermal protein profiling (TPP) and identified EYA3 as a stabilized protein in cells upon lagunamide A treatment. EYA3, involved in the DNA damage repair process, was functionally investigated via siRNA based knockdown studies and corresponding effects of lagunamide A on DNA repair were confirmed. Furthermore, we showed that lagunamide A sensitized tumor cells to treatment with the drug doxorubicin highlighting a putative therapeutic strategy.

Original language	English
Journal	ChemBioChem
DOIs	https://doi.org/10.1002/cbic.202400024
State	Accepted/In press - 2024

Keywords

Affinity based protein profiling
DNA damage
Lagunamide A
thermal protein profiling
TPP

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/cbic.202400024

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title = "Thermal Proteome Profiling Reveals Insight to Antiproliferative and Pro-Apoptotic Effects of Lagunamide A in the Modulation of DNA Damage Repair",

abstract = "Lagunamide A is a biologically active natural product with a yet unidentified molecular mode of action. Cellular studies revealed that lagunamide A is a potent inhibitor of cancer cell proliferation, promotes apoptosis and causes mitochondrial dysfunction. To decipher the cellular mechanism responsible for these effects, we utilized thermal protein profiling (TPP) and identified EYA3 as a stabilized protein in cells upon lagunamide A treatment. EYA3, involved in the DNA damage repair process, was functionally investigated via siRNA based knockdown studies and corresponding effects of lagunamide A on DNA repair were confirmed. Furthermore, we showed that lagunamide A sensitized tumor cells to treatment with the drug doxorubicin highlighting a putative therapeutic strategy.",

keywords = "Affinity based protein profiling, DNA damage, Lagunamide A, thermal protein profiling, TPP",

author = "Yudong Hu and Dietrich Mostert and Christina Orgler and Oliver Andler and Hans Zischka and Uli Kazmaier and Vollmar, {Angelika M.} and Simone Braig and Sieber, {Stephan A.} and Stefan Zahler",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors. ChemBioChem published by Wiley-VCH GmbH.",

year = "2024",

doi = "10.1002/cbic.202400024",

language = "English",

journal = "ChemBioChem",

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T1 - Thermal Proteome Profiling Reveals Insight to Antiproliferative and Pro-Apoptotic Effects of Lagunamide A in the Modulation of DNA Damage Repair

AU - Hu, Yudong

AU - Mostert, Dietrich

AU - Orgler, Christina

AU - Andler, Oliver

AU - Zischka, Hans

AU - Kazmaier, Uli

AU - Vollmar, Angelika M.

AU - Braig, Simone

AU - Sieber, Stephan A.

AU - Zahler, Stefan

PY - 2024

Y1 - 2024

N2 - Lagunamide A is a biologically active natural product with a yet unidentified molecular mode of action. Cellular studies revealed that lagunamide A is a potent inhibitor of cancer cell proliferation, promotes apoptosis and causes mitochondrial dysfunction. To decipher the cellular mechanism responsible for these effects, we utilized thermal protein profiling (TPP) and identified EYA3 as a stabilized protein in cells upon lagunamide A treatment. EYA3, involved in the DNA damage repair process, was functionally investigated via siRNA based knockdown studies and corresponding effects of lagunamide A on DNA repair were confirmed. Furthermore, we showed that lagunamide A sensitized tumor cells to treatment with the drug doxorubicin highlighting a putative therapeutic strategy.

AB - Lagunamide A is a biologically active natural product with a yet unidentified molecular mode of action. Cellular studies revealed that lagunamide A is a potent inhibitor of cancer cell proliferation, promotes apoptosis and causes mitochondrial dysfunction. To decipher the cellular mechanism responsible for these effects, we utilized thermal protein profiling (TPP) and identified EYA3 as a stabilized protein in cells upon lagunamide A treatment. EYA3, involved in the DNA damage repair process, was functionally investigated via siRNA based knockdown studies and corresponding effects of lagunamide A on DNA repair were confirmed. Furthermore, we showed that lagunamide A sensitized tumor cells to treatment with the drug doxorubicin highlighting a putative therapeutic strategy.

KW - Affinity based protein profiling

KW - DNA damage

KW - Lagunamide A

KW - thermal protein profiling

KW - TPP

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DO - 10.1002/cbic.202400024

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SN - 1439-4227

JO - ChemBioChem

JF - ChemBioChem

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Thermal Proteome Profiling Reveals Insight to Antiproliferative and Pro-Apoptotic Effects of Lagunamide A in the Modulation of DNA Damage Repair

Abstract

Keywords

UN SDGs

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