Albendazole as a promising molecule for tumor control

作者：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^*

来源：Redox Biology, 2016, 10: 90-99.

DOI：10.1016/j.redox.2016.09.013

• Albendazole
• Antitumor
• Apoptosis
• Cell cycle arrest
• DNA fragmentation
• Oxidative stress

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 (EC50=44.9 for 24 h) and inhibited MCF-7 colony formation (similar to 67.5% at 5 mu M). Intracellular ROS levels increased with ABZ treatment (similar to 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 (similar to 32%) and survival time was elongated (similar to 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.

• 出版日期2016-12