Aloe-emodin as drug candidate for cancer therapy
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Nadire Özenver
- Mohamed Saeed
- Lütfiye Ömur Demirezer
- Thomas Efferth
- DOI
- 10.18632/oncotarget.24880
- eISSN
- 1949-2553
- Ausgabe der Veröffentlichung
- 25
- Zeitschrift
- Oncotarget
- Sprache
- en
- Online publication date
- 2018
- Paginierung
- 17770 - 17796
- Datum der Veröffentlichung
- 2018
- Status
- Published
- Herausgeber
- Impact Journals, LLC
- Herausgeber URL
- http://dx.doi.org/10.18632/oncotarget.24880
- Datum der Datenerfassung
- 2020
- Titel
- Aloe-emodin as drug candidate for cancer therapy
- Ausgabe der Zeitschrift
- 9
Data source: Crossref
- Other metadata sources:
-
- Abstract
- As a leading cause of global mortality, cancer frequently cannot be cured due to the development of drug resistance. Therefore, novel drugs are required. Naturally occurring anthraquinones are mostly present in <i>Rumex</i> and <i>Rhamnus</i> species and are of interest because of their structural similarity to anthracyclines as well established anticancer drugs. In the present study, we focused on the structural elucidation of phytochemicals from <i>R. acetosella</i> as well as the investigation of cytotoxicity and modes of action of the main anthraquinone aglycons (emodin, Aloe-emodin, physcion, rhein). Resazurin reduction and protease viability marker assays were conducted to test their cytotoxicity. Microarray-based gene expression profiling was performed to identify cellular pathways affected by the compounds, which was validated by qPCR analyses and functional assays. Flow cytometry was used to measure cell cycle distribution, apoptosis and necrosis, induction of reactive oxygen species (ROS) and disruption of mitochondrial membrane potential (MMP). The comet assay was used to detect DNA damage. Aloe-emodin as the most cytotoxic compound revealed IC<sub>50</sub> values from 9.872 μM to 22.3 μM in drug-sensitive wild-type cell lines and from 11.19 μM to 33.76 μM in drug-resistant sublines, was selected to investigate its mechanism against cancer. Aloe-emodin-induced S phase arrest, ROS generation, DNA damage and apoptosis. Microarray hybridization revealed a profile of deregulated genes in Aloe-emodin-treated CCRF-CEM cells with diverse functions such as cell death and survival, cellular growth and proliferation, cellular development, gene expression, cellular function and maintenance. Aloe-emodin as well as <i>R. acetosella</i> deserve further investigations as possible antineoplastic drug candidates.
- Addresses
- Department of Pharmacognosy, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey.
- Autoren
- Nadire Özenver
- Mohamed Saeed
- Lütfiye Ömur Demirezer
- Thomas Efferth
- Thomas Efferth
- DOI
- 10.18632/oncotarget.24880
- eISSN
- 1949-2553
- Externe Identifier
- PubMed Identifier: 29707146
- PubMed Central ID: PMC5915154
- Open access
- true
- ISSN
- 1949-2553
- Ausgabe der Veröffentlichung
- 25
- Zeitschrift
- Oncotarget
- Sprache
- eng
- Medium
- Electronic-eCollection
- Online publication date
- 2018
- Open access status
- Open Access
- Paginierung
- 17770 - 17796
- Datum der Veröffentlichung
- 2018
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2018
- Titel
- Aloe-emodin as drug candidate for cancer therapy.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 9
Files
http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=24880&path%5B%5D=78011 https://europepmc.org/articles/PMC5915154?pdf=render
Data source: Europe PubMed Central
- Abstract
- As a leading cause of global mortality, cancer frequently cannot be cured due to the development of drug resistance. Therefore, novel drugs are required. Naturally occurring anthraquinones are mostly present in Rumex and Rhamnus species and are of interest because of their structural similarity to anthracyclines as well established anticancer drugs. In the present study, we focused on the structural elucidation of phytochemicals from R. acetosella as well as the investigation of cytotoxicity and modes of action of the main anthraquinone aglycons (emodin, Aloe-emodin, physcion, rhein). Resazurin reduction and protease viability marker assays were conducted to test their cytotoxicity. Microarray-based gene expression profiling was performed to identify cellular pathways affected by the compounds, which was validated by qPCR analyses and functional assays. Flow cytometry was used to measure cell cycle distribution, apoptosis and necrosis, induction of reactive oxygen species (ROS) and disruption of mitochondrial membrane potential (MMP). The comet assay was used to detect DNA damage. Aloe-emodin as the most cytotoxic compound revealed IC50 values from 9.872 μM to 22.3 μM in drug-sensitive wild-type cell lines and from 11.19 μM to 33.76 μM in drug-resistant sublines, was selected to investigate its mechanism against cancer. Aloe-emodin-induced S phase arrest, ROS generation, DNA damage and apoptosis. Microarray hybridization revealed a profile of deregulated genes in Aloe-emodin-treated CCRF-CEM cells with diverse functions such as cell death and survival, cellular growth and proliferation, cellular development, gene expression, cellular function and maintenance. Aloe-emodin as well as R. acetosella deserve further investigations as possible antineoplastic drug candidates.
- Date of acceptance
- 2018
- Autoren
- Nadire Özenver
- Mohamed Saeed
- Lütfiye Ömur Demirezer
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/29707146
- DOI
- 10.18632/oncotarget.24880
- eISSN
- 1949-2553
- Externe Identifier
- PubMed Central ID: PMC5915154
- Ausgabe der Veröffentlichung
- 25
- Zeitschrift
- Oncotarget
- Schlüsselwörter
- Aloe-emodin
- Rumex acetosella
- anthraquinone
- cancer
- multi-drug resistance
- Sprache
- eng
- Country
- United States
- Paginierung
- 17770 - 17796
- PII
- 24880
- Datum der Veröffentlichung
- 2018
- Status
- Published online
- Titel
- Aloe-emodin as drug candidate for cancer therapy.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 9
Data source: PubMed
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- Property of