Albendazole as a promising molecule for tumor control

This work evaluated the antitumor effects of albendazole (ABZ) and its relationship with modulation of oxidative stress and induction of DNA damage. The present results showed that ABZ causes oxidative cleavage on calf-thymus DNA suggesting that this compound can break DNA. ABZ treatment decreased M...

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Bibliographic Details
Published in:	Redox biology Vol. 10; no. C; pp. 90 - 99
Main Authors:	Castro, L S E P W, Kviecinski, M R, Ourique, F, Parisotto, E B, Grinevicius, V M A S, Correia, J F G, Wilhelm Filho, D, Pedrosa, R C
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier 01-12-2016
Subjects:	Albendazole Albendazole - administration & dosage Albendazole - pharmacology Animals Antineoplastic Agents - administration & dosage Antineoplastic Agents - pharmacology Antitumor Apoptosis Carcinoma, Ehrlich Tumor - drug therapy Carcinoma, Ehrlich Tumor - genetics Carcinoma, Ehrlich Tumor - metabolism Cell cycle arrest Cell Proliferation - drug effects Cell Survival - drug effects DNA Damage DNA fragmentation Drug Repositioning Humans MCF-7 Cells Membrane Potential, Mitochondrial - drug effects Mice Oxidative Stress Reactive Oxygen Species - metabolism Research Paper Xenograft Model Antitumor Assays Cell cycle arrest Oxidative stress Albendazole Antitumor DNA fragmentation Apoptosis
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Summary:	This work evaluated the antitumor effects of albendazole (ABZ) and its relationship with modulation of oxidative stress and induction of DNA damage. The present results showed that ABZ causes oxidative cleavage on calf-thymus DNA suggesting that this compound can break DNA. ABZ treatment decreased MCF-7 cell viability (EC =44.9 for 24h) and inhibited MCF-7 colony formation (~67.5% at 5μM). Intracellular ROS levels increased with ABZ treatment (~123%). The antioxidant NAC is able to revert the cytotoxic effects, ROS generation and loss of mitochondrial membrane potential of MCF-7 cells treated with ABZ. Ehrlich carcinoma growth was inhibited (~32%) and survival time was elongated (~50%) in animals treated with ABZ. Oxidative biomarkers (TBARS and protein carbonyl levels) and activity of antioxidant enzymes (CAT, SOD and GR) increased, and reduced glutathione (GSH) was depleted in animals treated with ABZ, indicating an oxidative stress condition, leading to a DNA damage causing phosphorylation of histone H2A variant, H2AX, and triggering apoptosis signaling, which was confirmed by increasing Bax/Bcl-xL rate, p53 and Bax expression. We propose that ABZ induces oxidative stress promoting DNA fragmentation and triggering apoptosis and inducing cell death, making this drug a promising leader molecule for development of new antitumor drugs.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2213-2317 2213-2317
DOI:	10.1016/j.redox.2016.09.013