Antiproliferative effect of benzimidazole anthelmintics albendazole, ricobendazole, and flubendazole in intestinal cancer cell lines
Language English Country Great Britain, England Media print
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Adenocarcinoma drug therapy MeSH
- Albendazole analogs & derivatives pharmacology MeSH
- Anthelmintics pharmacology MeSH
- Antineoplastic Agents, Phytogenic pharmacology MeSH
- Antineoplastic Agents pharmacology MeSH
- Drug Resistance, Neoplasm drug effects MeSH
- G2 Phase drug effects MeSH
- Inhibitory Concentration 50 MeSH
- Humans MeSH
- Mebendazole analogs & derivatives pharmacology MeSH
- Microtubules drug effects MeSH
- Tubulin Modulators pharmacology MeSH
- Cell Line, Tumor MeSH
- Paclitaxel pharmacology MeSH
- Cell Proliferation drug effects MeSH
- Protein Stability drug effects MeSH
- Intestinal Neoplasms drug therapy MeSH
- Drug Synergism MeSH
- Cell Survival drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Albendazole MeSH
- albendazole sulfoxide MeSH Browser
- Anthelmintics MeSH
- Antineoplastic Agents, Phytogenic MeSH
- Antineoplastic Agents MeSH
- flubendazole MeSH Browser
- Mebendazole MeSH
- Tubulin Modulators MeSH
- Paclitaxel MeSH
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.
References provided by Crossref.org
Biological Activity and Molecular Structures of Bis(benzimidazole) and Trithiocyanurate Complexes