Albendazole as a promising molecule for tumor control

Abstract

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 (~67.5% at 5 μM). 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.

Repositioning of Anti-parasitic Drugs in Cyclodextrin Inclusion Complexes for Treatment of Triple-Negative Breast Cancer

“…For this reason, we decided to focus our studies on the antitumor effect of ABZ. A recent study in a breast cancer model (MCF-7 cells) showed that ABZ inhibited cell viability [1]. Nevertheless, it is worthwhile to note that we obtained the same results in a more aggressive model.…”

“…Cancer is a major cause of mortality worldwide despite of the large number of treatment and prevention studies. According to the World Health Organization estimates, by 2030, the global incidence is expected to increase to 21.7 million cancer cases [1][2][3]. Currently, chemotherapy is one of the most effective strategies to avoid the proliferation of malignant tumors [3,4].…”

“…Currently, chemotherapy is one of the most effective strategies to avoid the proliferation of malignant tumors [3,4]. However, the ability of cancer cells to become resistant to different drugs remains a significant impediment to successful chemotherapy [1]. In this sense, drug repositioning has emerged as an alternative strategy for cancer treatment.…”

“…Research on ABZ antitumor activity has been carried out on ovarian cancer cell lines [23,24], and other studies were performed on HCT-116 (a colorectal cancer cell line) in which ABZ was formulated as hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complexes [25,26]. Castro et al (2016) reported an interesting study on MCF7 breast cancer cells, showing that ABZ promotes oxidative DNA damage, which induces DNA fragmentation, apoptosis, and cell death [1]. In addition, Sorlie et al (2003) described the effect of ABZ on MCF7, an estrogen receptorpositive cell line, extending the putative use of ABZ for the treatment of triple-negative breast tumors, the type of breast cancer with worse associated prognosis and limited therapeutic options [27,28].…”

The Benzimidazole-Based Anthelmintic Parbendazole: A Repurposed Drug Candidate That Synergizes with Gemcitabine in Pancreatic Cancer

“…Some members of benzimidazole-based anthelmintic family, such as albendazole, mebendazole and flubendazole, are being considered for repurposing in cancer therapy [12]. These drugs are widely used in animals and humans as safe and effective treatments for intestinal parasites [13][14][15], but there is also evidence of their antitumor effects in melanoma, leukemia, medulloblastoma, breast and colorectal cancers [16][17][18][19][20][21][22]. Interestingly, very little is known about the effects of these drugs in PC.…”