Fenben (sometimes referred to as “Fenbe” or ”FenBen”) is an antiworm drug belonging to the benzimidazole carbamate family and has been in use as a broad-spectrum anthelmintic for over six decades. It is very effective against parasites such as Ascaris and hookworms. It is also safe for long term use in humans.
It was recently reported that fenbendazole (FZ) has antitumor and radiosensitizing effects in cancer cells. In particular, it inhibits microtubule dynamics and induces p53 activation in tumor cells, both of which contribute to its antitumor effects. Moreover, it inhibits glucose uptake in cancer cells by down regulation of the GLUT transporters and key glycolytic enzymes.
In the present study, we investigated whether or not fenbendazole acts as a radiation sensitizer in human lung cancer cell lines by comparing the survival of hypoxic and aerobic cultures treated with graded doses of radiation and assayed using a colony formation assay. We found that FZ did not alter the radiation dose-response curve in hypoxic cells. However, incubation with FZ for 2 h did lead to a significant decrease in the viability of hypoxic cultures.
In addition, a FZ-treated culture of human A549 lung adenocarcinoma cells showed a significant decrease in polymerized tubulin as assessed by immunofluorescence and spectrophotometry. Moreover, a FZ treatment of human A549 cells under severe hypoxia altered the microtubule network by distorting its organization, and these changes were reversed upon colchicine treatment. These data suggest that the mechanism of fenbendazole-mediated radiation sensitization is through a distortion in tubulin structure. fenben
