Cytotoxicity of apigenin toward multiple myeloma cell lines and suppression of iNOS and COX-2 expression in STAT1-transfected HEK293 cells
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Aveen N Adham
- Sara Abdelfatah
- Alaadin M Naqishbandi
- Nuha Mahmoud
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000592920900014&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1016/j.phymed.2020.153371
- eISSN
- 1618-095X
- Externe Identifier
- Clarivate Analytics Document Solution ID: OW5IU
- PubMed Identifier: 33070080
- ISSN
- 0944-7113
- Zeitschrift
- PHYTOMEDICINE
- Schlüsselwörter
- Bioinformatic analysis
- Flavonoid
- Isobologram analysis
- Multiple myeloma
- Molecular modes of action
- STAT1
- Artikelnummer
- ARTN 153371
- Datum der Veröffentlichung
- 2021
- Status
- Published
- Titel
- Cytotoxicity of apigenin toward multiple myeloma cell lines and suppression of iNOS and COX-2 expression in STAT1-transfected HEK293 cells
- Sub types
- Article
- Ausgabe der Zeitschrift
- 80
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Aveen N Adham
- Sara Abdelfatah
- Alaadin M Naqishbandi
- Nuha Mahmoud
- Thomas Efferth
- DOI
- 10.1016/j.phymed.2020.153371
- ISSN
- 0944-7113
- Zeitschrift
- Phytomedicine
- Sprache
- en
- Artikelnummer
- 153371
- Paginierung
- 153371 - 153371
- Datum der Veröffentlichung
- 2021
- Status
- Published
- Herausgeber
- Elsevier BV
- Herausgeber URL
- http://dx.doi.org/10.1016/j.phymed.2020.153371
- Datum der Datenerfassung
- 2021
- Titel
- Cytotoxicity of apigenin toward multiple myeloma cell lines and suppression of iNOS and COX-2 expression in STAT1-transfected HEK293 cells
- Ausgabe der Zeitschrift
- 80
Data source: Crossref
- Abstract
- <h4>Background</h4>Apigenin is one of the most abundant dietary flavonoids that possesses multiple bio-functions.<h4>Purpose</h4>This study was designed to determine the influence of apigenin on gene expressions, cancer cells, as well as STAT1/COX-2/iNOS pathway mediated inflammation and tumorigenesis in HEK293-STAT1 cells. Furthermore, the cytotoxic activity toward multiple myeloma (MM) cell lines was investigated.<h4>Methods</h4>Bioinformatic analyses were used to predict the sensitivity and resistance of tumor cells toward apigenin and to determine cellular pathways influenced by this compound. The cytotoxic and ferroptotic activity of apigenin was examined by the resazurin reduction assay. Additionally, we evaluated apoptosis, and cell cycle distribution, induction of reactive oxygen species (ROS) and loss of integrity of mitochondrial membrane (MMP) by using the flow cytometry analysis. DAPI staining was used to detect characteristic apoptotic features. Furthermore, we verified its anti-inflammatory and additional mechanism of cell death by western blotting.<h4>Results</h4>COMPARE and hierarchical cluster analyses exhibited that 29 of 55 tumor cell lines were sensitive against apigenin (p < 0.001). The Ingenuity Pathway Analysis data showed that important bio-functions affected by apigenin were: gene expression, cancer, hematological system development and function, inflammatory response, and cell cycle. The STAT1 transcription factor was chosen as target protein on the basis of gene promoter binding motif analyses. Apigenin blocked cell proliferation of wild-type HEK293 and STAT1 reporter cells (HEK293-STAT1), promoted STAT1 suppression and subsequent COX-2 and iNOS inhibition. Apigenin also exhibited synergistic activity in combination with doxorubicin toward HEK293-STAT1 cells. Apigenin exerted excellent growth-inhibitory activity against MM cells in a concentration-dependent manner with the greatest activity toward NCI-H929 (IC<sub>50</sub> value: 10.73 ± 3.21 μM). Apigenin induced apoptosis, cell cycle arrest, ferroptosis and autophagy in NCI-H929 cells.<h4>Conclusion</h4>Apigenin may be a suitable candidate for MM treatment. The inhibition of the STAT1/COX-2/iNOS signaling pathway by apigenin is an important mechanism not only in the suppression of inflammation but also in induction of apoptosis.
- Addresses
- Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Erbil, Kurdistan Region, Iraq; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
- Autoren
- Aveen N Adham
- Sara Abdelfatah
- Alaadin M Naqishbandi
- Nuha Mahmoud
- Thomas Efferth
- DOI
- 10.1016/j.phymed.2020.153371
- eISSN
- 1618-095X
- Externe Identifier
- PubMed Identifier: 33070080
- Open access
- false
- ISSN
- 0944-7113
- Zeitschrift
- Phytomedicine : international journal of phytotherapy and phytopharmacology
- Schlüsselwörter
- Cell Line, Tumor
- Humans
- Multiple Myeloma
- Reactive Oxygen Species
- Apigenin
- Doxorubicin
- Antineoplastic Agents, Phytogenic
- Antineoplastic Combined Chemotherapy Protocols
- Computational Biology
- Cell Cycle
- Apoptosis
- Cell Proliferation
- Dose-Response Relationship, Drug
- Autophagy
- STAT1 Transcription Factor
- Cyclooxygenase 2
- Nitric Oxide Synthase Type II
- HEK293 Cells
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2020
- Paginierung
- 153371
- Datum der Veröffentlichung
- 2021
- Status
- Published
- Datum der Datenerfassung
- 2020
- Titel
- Cytotoxicity of apigenin toward multiple myeloma cell lines and suppression of iNOS and COX-2 expression in STAT1-transfected HEK293 cells.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 80
Data source: Europe PubMed Central
- Abstract
- BACKGROUND: Apigenin is one of the most abundant dietary flavonoids that possesses multiple bio-functions. PURPOSE: This study was designed to determine the influence of apigenin on gene expressions, cancer cells, as well as STAT1/COX-2/iNOS pathway mediated inflammation and tumorigenesis in HEK293-STAT1 cells. Furthermore, the cytotoxic activity toward multiple myeloma (MM) cell lines was investigated. METHODS: Bioinformatic analyses were used to predict the sensitivity and resistance of tumor cells toward apigenin and to determine cellular pathways influenced by this compound. The cytotoxic and ferroptotic activity of apigenin was examined by the resazurin reduction assay. Additionally, we evaluated apoptosis, and cell cycle distribution, induction of reactive oxygen species (ROS) and loss of integrity of mitochondrial membrane (MMP) by using the flow cytometry analysis. DAPI staining was used to detect characteristic apoptotic features. Furthermore, we verified its anti-inflammatory and additional mechanism of cell death by western blotting. RESULTS: COMPARE and hierarchical cluster analyses exhibited that 29 of 55 tumor cell lines were sensitive against apigenin (p < 0.001). The Ingenuity Pathway Analysis data showed that important bio-functions affected by apigenin were: gene expression, cancer, hematological system development and function, inflammatory response, and cell cycle. The STAT1 transcription factor was chosen as target protein on the basis of gene promoter binding motif analyses. Apigenin blocked cell proliferation of wild-type HEK293 and STAT1 reporter cells (HEK293-STAT1), promoted STAT1 suppression and subsequent COX-2 and iNOS inhibition. Apigenin also exhibited synergistic activity in combination with doxorubicin toward HEK293-STAT1 cells. Apigenin exerted excellent growth-inhibitory activity against MM cells in a concentration-dependent manner with the greatest activity toward NCI-H929 (IC50 value: 10.73 ± 3.21 μM). Apigenin induced apoptosis, cell cycle arrest, ferroptosis and autophagy in NCI-H929 cells. CONCLUSION: Apigenin may be a suitable candidate for MM treatment. The inhibition of the STAT1/COX-2/iNOS signaling pathway by apigenin is an important mechanism not only in the suppression of inflammation but also in induction of apoptosis.
- Date of acceptance
- 2020
- Autoren
- Aveen N Adham
- Sara Abdelfatah
- Alaadin M Naqishbandi
- Nuha Mahmoud
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/33070080
- DOI
- 10.1016/j.phymed.2020.153371
- eISSN
- 1618-095X
- Zeitschrift
- Phytomedicine
- Schlüsselwörter
- Bioinformatic analysis
- Flavonoid
- Isobologram analysis
- Molecular modes of action
- Multiple myeloma
- STAT1
- Antineoplastic Agents, Phytogenic
- Antineoplastic Combined Chemotherapy Protocols
- Apigenin
- Apoptosis
- Autophagy
- Cell Cycle
- Cell Line, Tumor
- Cell Proliferation
- Computational Biology
- Cyclooxygenase 2
- Dose-Response Relationship, Drug
- Doxorubicin
- HEK293 Cells
- Humans
- Multiple Myeloma
- Nitric Oxide Synthase Type II
- Reactive Oxygen Species
- STAT1 Transcription Factor
- Sprache
- eng
- Country
- Germany
- Paginierung
- 153371
- PII
- S0944-7113(20)30202-6
- Datum der Veröffentlichung
- 2021
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2020
- Titel
- Cytotoxicity of apigenin toward multiple myeloma cell lines and suppression of iNOS and COX-2 expression in STAT1-transfected HEK293 cells.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 80
Data source: PubMed
- Beziehungen:
- Property of