Transcriptomics, molecular docking, and cross-resistance profiling of nobiletin in cancer cells and synergistic interaction with doxorubicin upon SOX5 transfection
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Aveen N Adham
- Sara Abdelfatah
- Alaadin Naqishbandi
- Yoshikazu Sugimoto
- Edmond Fleischer
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000795080100001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1016/j.phymed.2022.154064
- eISSN
- 1618-095X
- Externe Identifier
- Clarivate Analytics Document Solution ID: 1F3OJ
- PubMed Identifier: 35344715
- ISSN
- 0944-7113
- Zeitschrift
- PHYTOMEDICINE
- Schlüsselwörter
- Chemotherapy
- Microarray analysis
- Network pharmacology
- Phytochemical
- Transcriptomics
- Transcription factor
- Artikelnummer
- ARTN 154064
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Titel
- Transcriptomics, molecular docking, and cross-resistance profiling of nobiletin in cancer cells and synergistic interaction with doxorubicin upon SOX5 transfection
- Sub types
- Article
- Ausgabe der Zeitschrift
- 100
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Aveen N Adham
- Sara Abdelfatah
- Alaadin Naqishbandi
- Yoshikazu Sugimoto
- Edmond Fleischer
- Thomas Efferth
- DOI
- 10.1016/j.phymed.2022.154064
- ISSN
- 0944-7113
- Zeitschrift
- Phytomedicine
- Sprache
- en
- Artikelnummer
- 154064
- Paginierung
- 154064 - 154064
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Herausgeber
- Elsevier BV
- Herausgeber URL
- http://dx.doi.org/10.1016/j.phymed.2022.154064
- Datum der Datenerfassung
- 2023
- Titel
- Transcriptomics, molecular docking, and cross-resistance profiling of nobiletin in cancer cells and synergistic interaction with doxorubicin upon SOX5 transfection
- Ausgabe der Zeitschrift
- 100
Data source: Crossref
- Abstract
- <h4>Background</h4>Nobiletin is a polymethoxylated flavone from citrus fruit peels. Among other bioactivities, it acts antioxidative, anti-inflammatory, neuroprotective, and cardiovascular-protective. Nobiletin exerts profound anticancer activity in vitro and in vivo but the underlying mechanisms are not well understood.<h4>Purpose</h4>The aim was to unravel the multiple modes of action against cancer cells by bioinformatic and transcriptomic techniques and their verification by molecular pharmacological methods.<h4>Methods</h4>The in silico methods used were COMPARE analysis of transcriptomic data, signaling pathway analysis, transcription factor binding motif analysis in promoter sequences of target genes, and molecular docking. The in vitro methods used were resazurin assay, isobologram analysis, generation of stably SOX5-tranfected cells, and Western blotting.<h4>Results</h4>Nobiletin was cytotoxic against a wide range of cell lines from different tumor types, including diverse phenotypes to established anticancer drugs (e.g., P-glycoprotein, ABCB5, p53, EGFR). Cross-resistance profiling with 83 standard anticancer drugs revealed a correlation to antihormonal anticancer drugs, which can be explained by the phytoestrogenic features of nobiletin. Transcriptomic analysis showed that the responsiveness of tumor cells was predictable by their specific mRNA expression profile. Nobiletin bound to the transcription factor SOX5 in silico. SOX5 conferred resistance to the control drug doxorubicin but collateral sensitivity to nobiletin in HEK293 cells transfected with a lentiviral GFP-tagged pLOCORF-SOX5 vector. The combination of nobiletin and doxorubicin synergistically killed HEK293-SOX5 cells in isobologram analyses, implying attractive new treatment options.<h4>Conclusion</h4>Nobiletin represents an interesting candidate for cancer therapy with broad-spectrum activity and multiple modes of action. The identification of novel targets (i.e., SOX5) may allow its use for targeted tumor therapy in individualized treatment protocols.
- Addresses
- Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Erbil 44001, Kurdistan Region, Iraq.
- Autoren
- Aveen N Adham
- Sara Abdelfatah
- Alaadin Naqishbandi
- Yoshikazu Sugimoto
- Edmond Fleischer
- Thomas Efferth
- DOI
- 10.1016/j.phymed.2022.154064
- eISSN
- 1618-095X
- Externe Identifier
- PubMed Identifier: 35344715
- Open access
- false
- ISSN
- 0944-7113
- Zeitschrift
- Phytomedicine : international journal of phytotherapy and phytopharmacology
- Schlüsselwörter
- Cell Line, Tumor
- Humans
- Neoplasms
- Flavones
- Doxorubicin
- Transcription Factors
- Transfection
- SOXD Transcription Factors
- HEK293 Cells
- Transcriptome
- Molecular Docking Simulation
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2022
- Paginierung
- 154064
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Datum der Datenerfassung
- 2022
- Titel
- Transcriptomics, molecular docking, and cross-resistance profiling of nobiletin in cancer cells and synergistic interaction with doxorubicin upon SOX5 transfection.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 100
Data source: Europe PubMed Central
- Abstract
- BACKGROUND: Nobiletin is a polymethoxylated flavone from citrus fruit peels. Among other bioactivities, it acts antioxidative, anti-inflammatory, neuroprotective, and cardiovascular-protective. Nobiletin exerts profound anticancer activity in vitro and in vivo but the underlying mechanisms are not well understood. PURPOSE: The aim was to unravel the multiple modes of action against cancer cells by bioinformatic and transcriptomic techniques and their verification by molecular pharmacological methods. METHODS: The in silico methods used were COMPARE analysis of transcriptomic data, signaling pathway analysis, transcription factor binding motif analysis in promoter sequences of target genes, and molecular docking. The in vitro methods used were resazurin assay, isobologram analysis, generation of stably SOX5-tranfected cells, and Western blotting. RESULTS: Nobiletin was cytotoxic against a wide range of cell lines from different tumor types, including diverse phenotypes to established anticancer drugs (e.g., P-glycoprotein, ABCB5, p53, EGFR). Cross-resistance profiling with 83 standard anticancer drugs revealed a correlation to antihormonal anticancer drugs, which can be explained by the phytoestrogenic features of nobiletin. Transcriptomic analysis showed that the responsiveness of tumor cells was predictable by their specific mRNA expression profile. Nobiletin bound to the transcription factor SOX5 in silico. SOX5 conferred resistance to the control drug doxorubicin but collateral sensitivity to nobiletin in HEK293 cells transfected with a lentiviral GFP-tagged pLOCORF-SOX5 vector. The combination of nobiletin and doxorubicin synergistically killed HEK293-SOX5 cells in isobologram analyses, implying attractive new treatment options. CONCLUSION: Nobiletin represents an interesting candidate for cancer therapy with broad-spectrum activity and multiple modes of action. The identification of novel targets (i.e., SOX5) may allow its use for targeted tumor therapy in individualized treatment protocols.
- Date of acceptance
- 2022
- Autoren
- Aveen N Adham
- Sara Abdelfatah
- Alaadin Naqishbandi
- Yoshikazu Sugimoto
- Edmond Fleischer
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/35344715
- DOI
- 10.1016/j.phymed.2022.154064
- eISSN
- 1618-095X
- Zeitschrift
- Phytomedicine
- Schlüsselwörter
- Chemotherapy
- Microarray analysis
- Network pharmacology
- Phytochemical
- Transcription factor
- Transcriptomics
- Cell Line, Tumor
- Doxorubicin
- Flavones
- HEK293 Cells
- Humans
- Molecular Docking Simulation
- Neoplasms
- SOXD Transcription Factors
- Transcription Factors
- Transcriptome
- Transfection
- Sprache
- eng
- Country
- Germany
- Paginierung
- 154064
- PII
- S0944-7113(22)00142-8
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2022
- Titel
- Transcriptomics, molecular docking, and cross-resistance profiling of nobiletin in cancer cells and synergistic interaction with doxorubicin upon SOX5 transfection.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 100
Data source: PubMed
- Beziehungen:
- Property of