title: Antiproliferative effect of benzimidazole anthelmintics albendazole, ricobendazole, and flubendazole in intestinal cancer cell lines.
abstract: This study aimed to test the antiproliferative effect of three benzimidazole anthelmintics in intestinal cancer cells and to investigate whether these drugs, which inhibit tubulin polymerization, can potentiate the efficacy of the microtubule-stabilizing drug paclitaxel (PTX). Four intestinal cancer cell lines, SW480, SW620, HCT8, and Caco2, with different origins and growth characteristics were used. The antiproliferative effect of albendazole (ABZ), ricobendazole (RBZ), flubendazole (FLU), and their combinations with PTX was tested using three different end-point viability assays, cell cycle distribution analysis, and the x-CELLigence System for real-time cell analysis. ABZ and FLU inhibited cell proliferation significantly in a concentration-dependent and time-dependent manner through cell arrest in the G2/M phase. RBZ was not effective at any concentration tested. The cell lines differed in sensitivity to FLU and ABZ, with HCT8 being the most sensitive, showing IC₅₀ values for ABZ and FLU that reached 0.3 and 0.9 μmol/l, respectively. Combinations of PTX+ABZ and PTX+FLU decreased cell viability more effectively when compared with treatment with individual drugs alone. The anthelmintic benzimidazole drugs ABZ and FLU show a significant cytostatic effect and potentiate the efficacy of PTX in intestinal cancer cells.
authors.affiliation: Department of Medical Biology and Genetics, Faculty of Medicine, Charles University in Prague, Hradec Králové, Czech Republic. kralovav@lfhk.cuni.cz
authors.forename: Věra
authors.initials: V
authors.lastname: Králová
authors.forename: Veronika
authors.initials: V
authors.lastname: Hanušová
authors.forename: Petra
authors.initials: P
authors.lastname: Staňková
authors.forename: Kateřina
authors.initials: K
authors.lastname: Knoppová
authors.forename: Kristýna
authors.initials: K
authors.lastname: Čáňová
authors.forename: Lenka
authors.initials: L
authors.lastname: Skálová
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D015766:Albendazole / Q000031:analogs & derivatives / Q000494:pharmacology*; D000871:Anthelmintics / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004357:Drug Synergism; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D007414:Intestinal Neoplasms / Q000188:drug therapy*; D008463:Mebendazole / Q000031:analogs & derivatives* / Q000494:pharmacology; D008870:Microtubules / Q000187:drug effects; D017239:Paclitaxel / Q000494:pharmacology; D055550:Protein Stability / Q000187:drug effects; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D000871:Anthelmintics; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D050257:Tubulin Modulators; D008463:Mebendazole; D015766:Albendazole; C027186:albendazole sulfoxide; D017239:Paclitaxel; C018945:flubendazole