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.
Highlights
Albendazole (ABZ) is a microtubule-targeting anthelmintic with a remarkable activity against a variety of human cancer cells
Combination therapy with Microtubule-targeting agents (MTAs) may reduce the toxicity associated with the use of one agent at its maximum tolerated dose (MTD)
ABZ synergizes with colchicine In both HCT-116 and DU145 cells, the combination of ABZ and PTX were antagonistic, as combination index (CI) values were consistently above 1 (Figure 1A and 1B)
Summary
Albendazole (ABZ) is a microtubule-targeting anthelmintic with a remarkable activity against a variety of human cancer cells. We examined if the antitumor activity of ABZ could be enhanced by its combination with other microtubule-binding agents. The aims of using drug combinations are to increase efficacy, to reduce the dose and the toxicity, and to minimize or delay drug resistance [1]. Microtubule-targeting agents (MTAs) are among the most promising classes of the drugs in cancer therapy. Combination therapy with MTAs may reduce the toxicity associated with the use of one agent at its maximum tolerated dose (MTD). Combining low doses of chemotherapeutic agents at close regular intervals may enhance efficacy while reducing the toxicity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
