Combination of Albendazole and 2-Methoxyestradiol significantly improves the survival of HCT-116 tumor-bearing nude mice

Abstract

BackgroundAlbendazole (ABZ) is a microtubule-targeting anthelmintic with a remarkable activity against a variety of human cancer cells. In this study, we examined if the antitumor activity of ABZ could be enhanced by its combination with other microtubule-binding agents.MethodsThe interactions between ABZ and microtubule-binding agents, paclitaxel, vinblastine, colchicine, and 2-methoxyestradiol were characterized using median effect analysis method in HCT-116 colorectal cancer cells and DU145 prostate cancer cell line. The mechanism underlying the synergistic interaction related to tubulin polymerization and apoptosis was then investigated. Finally, the effect of the combination therapy on the survival of HCT-116 tumor-bearing nude mice was evaluated.ResultsAmong the tested drugs, a synergistic anti-proliferative effect was observed with the combination of low concentrations of ABZ plus colchicine and ABZ plus 2-methoxyestradiol (2ME). Exploring the mechanism of the interaction between ABZ and 2ME revealed that the combination therapy synergistically activated the extrinsic pathway of apoptosis. Consistent with in vitro results, the combination of low concentration of ABZ with 2ME prolonged the survival of mice-bearing HCT-116 tumors. High concentration of ABZ in combination with 2ME, however, proved to be less effective than ABZ alone.ConclusionsThe combination of low doses of ABZ and 2ME has shown promising results in our pre-clinical model. Additionally, the finding that the combination of two microtubule-binding agents that share the same binding site can act synergistically may lead to the development of new therapeutic strategies in cancer treatment.

Up‐regulation of survivin by AKT and hypoxia‐inducible factor 1α contributes to cisplatin resistance in gastric cancer

“…The groups received intraperitoneal injections of 200 lL NaCl/P i , CDDP (10 mgÁkg À1 ), YM155 (3 mgÁkg À1 ) or TCN (2 mgÁkg À1 ) every 3 days, or 2ME2 (25 mgÁkg À1 ) daily, or various combinations as indicated. The doses for each reagent used in the study have previously been reported to be effective in mice [32,44,45]. Mice were killed on day 15.…”

“…The doses for each reagent used in the study have previously been reported to be effective in mice [32,44,45]. Mice were killed on day 15.…”

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

“…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].…”

Protective Effect of Sika Deer (Cervus nippon) Velvet Antler Extract against Cisplatin-Induced Kidney and Liver Injury in a Prostate Cancer PC-3 Cell Xenograft Model

“…At the end of the treatment, the gavage tube was left in place for several seconds to avoid regurgitation and ensure the total calculated dose was administered. e tumor sizes were monitored every 2 days using a digital caliper, and the tumor volumes were calculated using the formula: L × S 2 × 0.5, where L and S represent the longest and shortest tumor diameters, respectively [31]. e mice were also weighed.…”