Pharmacogenomics of Scopoletin in Tumor Cells
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Ean-Jeong Seo
- Mohamed Saeed
- Betty Yuen Kwan Law
- An Guo Wu
- Onat Kadioglu
- Henry Johannes Greten
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000375155000107&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.3390/molecules21040496
- Externe Identifier
- Clarivate Analytics Document Solution ID: DK8CO
- PubMed Identifier: 27092478
- ISSN
- 1420-3049
- Ausgabe der Veröffentlichung
- 4
- Zeitschrift
- MOLECULES
- Schlüsselwörter
- ABC-transporter
- cluster analysis
- coumarin
- herbal medicine
- microarrays
- multidrug resistance
- phytotherapy
- Artikelnummer
- ARTN 496
- Datum der Veröffentlichung
- 2016
- Status
- Published
- Titel
- Pharmacogenomics of Scopoletin in Tumor Cells
- Sub types
- Article
- Ausgabe der Zeitschrift
- 21
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Ean-Jeong Seo
- Mohamed Saeed
- Betty Law
- An Wu
- Onat Kadioglu
- Henry Greten
- Thomas Efferth
- DOI
- 10.3390/molecules21040496
- eISSN
- 1420-3049
- Ausgabe der Veröffentlichung
- 4
- Zeitschrift
- Molecules
- Sprache
- en
- Online publication date
- 2016
- Paginierung
- 496 - 496
- Status
- Published online
- Herausgeber
- MDPI AG
- Herausgeber URL
- http://dx.doi.org/10.3390/molecules21040496
- Datum der Datenerfassung
- 2022
- Titel
- Pharmacogenomics of Scopoletin in Tumor Cells
- Ausgabe der Zeitschrift
- 21
Data source: Crossref
- Abstract
- Drug resistance and the severe side effects of chemotherapy necessitate the development of novel anticancer drugs. Natural products are a valuable source for drug development. Scopoletin is a coumarin compound, which can be found in several Artemisia species and other plant genera. Microarray-based RNA expression profiling of the NCI cell line panel showed that cellular response of scopoletin did not correlate to the expression of ATP-binding cassette (ABC) transporters as classical drug resistance mechanisms (ABCB1, ABCB5, ABCC1, ABCG2). This was also true for the expression of the oncogene EGFR and the mutational status of the tumor suppressor gene, TP53. However, mutations in the RAS oncogenes and the slow proliferative activity in terms of cell doubling times significantly correlated with scopoletin resistance. COMPARE and hierarchical cluster analyses of transcriptome-wide mRNA expression resulted in a set of 40 genes, which all harbored binding motifs in their promoter sequences for the transcription factor, NF-κB, which is known to be associated with drug resistance. RAS mutations, slow proliferative activity, and NF-κB may hamper its effectiveness. By in silico molecular docking studies, we found that scopoletin bound to NF-κB and its regulator IκB. Scopoletin activated NF-κB in a SEAP-driven NF-κB reporter cell line, indicating that NF-κB might be a resistance factor for scopoletin. In conclusion, scopoletin might serve as lead compound for drug development because of its favorable activity against tumor cells with ABC-transporter expression, although NF-κB activation may be considered as resistance factor for this compound. Further investigations are warranted to explore the full therapeutic potential of this natural product.
- Addresses
- Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Staudinger Weg 5, 55128 Mainz, Germany. seo@uni-mainz.de.
- Autoren
- Ean-Jeong Seo
- Mohamed Saeed
- Betty Yuen Kwan Law
- An Guo Wu
- Onat Kadioglu
- Henry Johannes Greten
- Thomas Efferth
- Thomas Efferth
- DOI
- 10.3390/molecules21040496
- eISSN
- 1420-3049
- Externe Identifier
- PubMed Identifier: 27092478
- PubMed Central ID: PMC6273985
- Open access
- true
- ISSN
- 1420-3049
- Ausgabe der Veröffentlichung
- 4
- Zeitschrift
- Molecules (Basel, Switzerland)
- Schlüsselwörter
- Cell Line, Tumor
- Humans
- Artemisia
- Neoplasms
- Scopoletin
- ATP-Binding Cassette Transporters
- NF-kappa B
- Plant Extracts
- Protein Array Analysis
- Pharmacogenetics
- Drug Resistance, Multiple
- Signal Transduction
- Gene Expression Regulation, Neoplastic
- Drug Resistance, Neoplasm
- Transcription Factor RelA
- Molecular Docking Simulation
- Sprache
- eng
- Medium
- Electronic
- Online publication date
- 2016
- Open access status
- Open Access
- Paginierung
- 496
- Datum der Veröffentlichung
- 2016
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2016
- Titel
- Pharmacogenomics of Scopoletin in Tumor Cells.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 21
Files
https://www.mdpi.com/1420-3049/21/4/496/pdf?version=1460720667 https://europepmc.org/articles/PMC6273985?pdf=render
Data source: Europe PubMed Central
- Abstract
- Drug resistance and the severe side effects of chemotherapy necessitate the development of novel anticancer drugs. Natural products are a valuable source for drug development. Scopoletin is a coumarin compound, which can be found in several Artemisia species and other plant genera. Microarray-based RNA expression profiling of the NCI cell line panel showed that cellular response of scopoletin did not correlate to the expression of ATP-binding cassette (ABC) transporters as classical drug resistance mechanisms (ABCB1, ABCB5, ABCC1, ABCG2). This was also true for the expression of the oncogene EGFR and the mutational status of the tumor suppressor gene, TP53. However, mutations in the RAS oncogenes and the slow proliferative activity in terms of cell doubling times significantly correlated with scopoletin resistance. COMPARE and hierarchical cluster analyses of transcriptome-wide mRNA expression resulted in a set of 40 genes, which all harbored binding motifs in their promoter sequences for the transcription factor, NF-κB, which is known to be associated with drug resistance. RAS mutations, slow proliferative activity, and NF-κB may hamper its effectiveness. By in silico molecular docking studies, we found that scopoletin bound to NF-κB and its regulator IκB. Scopoletin activated NF-κB in a SEAP-driven NF-κB reporter cell line, indicating that NF-κB might be a resistance factor for scopoletin. In conclusion, scopoletin might serve as lead compound for drug development because of its favorable activity against tumor cells with ABC-transporter expression, although NF-κB activation may be considered as resistance factor for this compound. Further investigations are warranted to explore the full therapeutic potential of this natural product.
- Date of acceptance
- 2016
- Autoren
- Ean-Jeong Seo
- Mohamed Saeed
- Betty Yuen Kwan Law
- An Guo Wu
- Onat Kadioglu
- Henry Johannes Greten
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/27092478
- DOI
- 10.3390/molecules21040496
- eISSN
- 1420-3049
- Externe Identifier
- PubMed Central ID: PMC6273985
- Ausgabe der Veröffentlichung
- 4
- Zeitschrift
- Molecules
- Schlüsselwörter
- ABC-transporter
- cluster analysis
- coumarin
- herbal medicine
- microarrays
- multidrug resistance
- phytotherapy
- ATP-Binding Cassette Transporters
- Artemisia
- Cell Line, Tumor
- Drug Resistance, Multiple
- Drug Resistance, Neoplasm
- Gene Expression Regulation, Neoplastic
- Humans
- Molecular Docking Simulation
- NF-kappa B
- Neoplasms
- Pharmacogenetics
- Plant Extracts
- Protein Array Analysis
- Scopoletin
- Signal Transduction
- Transcription Factor RelA
- Sprache
- eng
- Country
- Switzerland
- Paginierung
- 496
- PII
- molecules21040496
- Datum der Veröffentlichung
- 2016
- Status
- Published online
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2016
- Titel
- Pharmacogenomics of Scopoletin in Tumor Cells.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 21
Data source: PubMed
- Beziehungen:
- Property of