Research Papers:

Aloe-emodin as drug candidate for cancer therapy

Nadire Özenver, Mohamed Saeed, Lütfiye Ömür Demirezer and Thomas Efferth _

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Oncotarget. 2018; 9:17770-17796. https://doi.org/10.18632/oncotarget.24880

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Nadire Özenver1, Mohamed Saeed2, Lütfiye Ömur Demirezer1 and Thomas Efferth2

1Department of Pharmacognosy, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey

2Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, 55128 Mainz, Germany

Correspondence to:

Thomas Efferth, email: [email protected]

Keywords: Aloe-emodin; Rumex acetosella; cancer; multi-drug resistance; anthraquinone

Received: June 27, 2017    Accepted: February 27, 2018    Published: April 03, 2018


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.

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