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Aloe-emodin as drug candidate for cancer therapy

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 a...

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Autores principales: Özenver, Nadire, Saeed, Mohamed, Demirezer, Lütfiye Ömur, Efferth, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915154/
https://www.ncbi.nlm.nih.gov/pubmed/29707146
http://dx.doi.org/10.18632/oncotarget.24880
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author Özenver, Nadire
Saeed, Mohamed
Demirezer, Lütfiye Ömur
Efferth, Thomas
author_facet Özenver, Nadire
Saeed, Mohamed
Demirezer, Lütfiye Ömur
Efferth, Thomas
author_sort Özenver, Nadire
collection PubMed
description 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 IC(50) 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.
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spelling pubmed-59151542018-04-27 Aloe-emodin as drug candidate for cancer therapy Özenver, Nadire Saeed, Mohamed Demirezer, Lütfiye Ömur Efferth, Thomas Oncotarget Research Paper 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 IC(50) 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. Impact Journals LLC 2018-04-03 /pmc/articles/PMC5915154/ /pubmed/29707146 http://dx.doi.org/10.18632/oncotarget.24880 Text en Copyright: © 2018 Özenver et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Özenver, Nadire
Saeed, Mohamed
Demirezer, Lütfiye Ömur
Efferth, Thomas
Aloe-emodin as drug candidate for cancer therapy
title Aloe-emodin as drug candidate for cancer therapy
title_full Aloe-emodin as drug candidate for cancer therapy
title_fullStr Aloe-emodin as drug candidate for cancer therapy
title_full_unstemmed Aloe-emodin as drug candidate for cancer therapy
title_short Aloe-emodin as drug candidate for cancer therapy
title_sort aloe-emodin as drug candidate for cancer therapy
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915154/
https://www.ncbi.nlm.nih.gov/pubmed/29707146
http://dx.doi.org/10.18632/oncotarget.24880
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