Synthetic cajanin stilbene acid derivatives inhibit c-MYC in breast cancer cells
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Onat Kadioglu
- Yujie Fu
- Benjamin Wiench
- Yuangang Zu
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000370343000007&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1007/s00204-015-1480-2
- eISSN
- 1432-0738
- Externe Identifier
- Clarivate Analytics Document Solution ID: DE0VJ
- PubMed Identifier: 25716159
- ISSN
- 0340-5761
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- ARCHIVES OF TOXICOLOGY
- Schlüsselwörter
- Breast cancer
- Cajanin stilbene acid
- c-MYC
- Microarray
- Pharmacogenomics
- Paginierung
- 575 - 588
- Datum der Veröffentlichung
- 2016
- Status
- Published
- Titel
- Synthetic cajanin stilbene acid derivatives inhibit c-MYC in breast cancer cells
- Sub types
- Article
- Ausgabe der Zeitschrift
- 90
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Onat Kadioglu
- Yujie Fu
- Benjamin Wiench
- Yuangang Zu
- Thomas Efferth
- DOI
- 10.1007/s00204-015-1480-2
- eISSN
- 1432-0738
- ISSN
- 0340-5761
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- Archives of Toxicology
- Sprache
- en
- Online publication date
- 2015
- Paginierung
- 575 - 588
- Datum der Veröffentlichung
- 2016
- Status
- Published
- Herausgeber
- Springer Science and Business Media LLC
- Herausgeber URL
- http://dx.doi.org/10.1007/s00204-015-1480-2
- Datum der Datenerfassung
- 2020
- Titel
- Synthetic cajanin stilbene acid derivatives inhibit c-MYC in breast cancer cells
- Ausgabe der Zeitschrift
- 90
Data source: Crossref
- Abstract
- In the present study, we investigated the activity and modes of action of cajanin stilbene acid (CSA) and its derivatives in terms of cytotoxicity, gene expression profile, and transcription factor activity. XTT assays on MCF7 cells were performed upon treatment with CSA or derivatives. After the determination of IC50 values, gene expression profiling was performed with Agilent microarray experiments. Deregulated genes were determined with Chipster software, pathway and functional analyses were performed with Ingenuity pathway software. In order to identify the potential upstream regulators, MatInspector software was used to perform transcription factor binding motif search in the promoter regions of the deregulated genes. Molecular docking on MYC/MAX complex and reporter cell line experiments were performed to validate the MYC inhibitory activity of CSA and its derivatives. Two known MYC inhibitors: 10058-F4 and 10074-G5 were used as positive control. All compounds showed cytotoxicities in the micromolar range. Microarray analyses pointed to cell cycle, DNA damage, and DNA repair as mainly affected cellular functions. Promoter motif analysis of the deregulated genes further supported the microarray gene expression analysis results emphasizing the relevance of transcription factors regulating cell cycle and proliferation, with MYC as being the most pronounced one. Luciferase-based reporter cell line experiments and molecular docking studies yielded supportive results emphasizing the inhibitory activity of CSA and its derivatives on MYC. CSA and its derivatives are shown to be promising anticancer compounds with low toxicity. They inhibit MYC activity comparable to 10058-F4 and 10074-G5. Further studies are warranted to analyze the therapeutic applicability of these compounds in more detail.
- Addresses
- Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128, Mainz, Germany.
- Autoren
- Onat Kadioglu
- Yujie Fu
- Benjamin Wiench
- Yuangang Zu
- Thomas Efferth
- Thomas Efferth
- DOI
- 10.1007/s00204-015-1480-2
- eISSN
- 1432-0738
- Externe Identifier
- PubMed Identifier: 25716159
- Open access
- false
- ISSN
- 0340-5761
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- Archives of toxicology
- Schlüsselwörter
- Humans
- Breast Neoplasms
- Salicylates
- Stilbenes
- Diethylstilbestrol
- Antineoplastic Agents
- Oligonucleotide Array Sequence Analysis
- Drug Screening Assays, Antitumor
- Gene Expression Profiling
- Gene Expression Regulation, Neoplastic
- Genes, myc
- Female
- Promoter Regions, Genetic
- MCF-7 Cells
- Molecular Docking Simulation
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2015
- Paginierung
- 575 - 588
- Datum der Veröffentlichung
- 2016
- Status
- Published
- Datum der Datenerfassung
- 2015
- Titel
- Synthetic cajanin stilbene acid derivatives inhibit c-MYC in breast cancer cells.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 90
Data source: Europe PubMed Central
- Abstract
- In the present study, we investigated the activity and modes of action of cajanin stilbene acid (CSA) and its derivatives in terms of cytotoxicity, gene expression profile, and transcription factor activity. XTT assays on MCF7 cells were performed upon treatment with CSA or derivatives. After the determination of IC50 values, gene expression profiling was performed with Agilent microarray experiments. Deregulated genes were determined with Chipster software, pathway and functional analyses were performed with Ingenuity pathway software. In order to identify the potential upstream regulators, MatInspector software was used to perform transcription factor binding motif search in the promoter regions of the deregulated genes. Molecular docking on MYC/MAX complex and reporter cell line experiments were performed to validate the MYC inhibitory activity of CSA and its derivatives. Two known MYC inhibitors: 10058-F4 and 10074-G5 were used as positive control. All compounds showed cytotoxicities in the micromolar range. Microarray analyses pointed to cell cycle, DNA damage, and DNA repair as mainly affected cellular functions. Promoter motif analysis of the deregulated genes further supported the microarray gene expression analysis results emphasizing the relevance of transcription factors regulating cell cycle and proliferation, with MYC as being the most pronounced one. Luciferase-based reporter cell line experiments and molecular docking studies yielded supportive results emphasizing the inhibitory activity of CSA and its derivatives on MYC. CSA and its derivatives are shown to be promising anticancer compounds with low toxicity. They inhibit MYC activity comparable to 10058-F4 and 10074-G5. Further studies are warranted to analyze the therapeutic applicability of these compounds in more detail.
- Date of acceptance
- 2015
- Autoren
- Onat Kadioglu
- Yujie Fu
- Benjamin Wiench
- Yuangang Zu
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/25716159
- DOI
- 10.1007/s00204-015-1480-2
- eISSN
- 1432-0738
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- Arch Toxicol
- Schlüsselwörter
- Breast cancer
- Cajanin stilbene acid
- Microarray
- Pharmacogenomics
- c-MYC
- Antineoplastic Agents
- Breast Neoplasms
- Diethylstilbestrol
- Drug Screening Assays, Antitumor
- Female
- Gene Expression Profiling
- Gene Expression Regulation, Neoplastic
- Genes, myc
- Humans
- MCF-7 Cells
- Molecular Docking Simulation
- Oligonucleotide Array Sequence Analysis
- Promoter Regions, Genetic
- Salicylates
- Stilbenes
- Sprache
- eng
- Country
- Germany
- Paginierung
- 575 - 588
- PII
- 10.1007/s00204-015-1480-2
- Datum der Veröffentlichung
- 2016
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2016
- Titel
- Synthetic cajanin stilbene acid derivatives inhibit c-MYC in breast cancer cells.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 90
Data source: PubMed
- Beziehungen:
- Property of