Fenben As a Radiosensitizer in Cancer Cells

Fenben (also known as Panacur) is a broad-spectrum anthelmintic compound of the benzimidazole family. It is used in veterinary medicine to treat various parasitic infections including gastrointestinal nematodes, lungworms and certain tapeworms. In humans, fenbendazole is taken orally to prevent intestinal parasites. Fenbendazole is also used as an antifungal agent to treat fungal infections.

In the present study, we investigated whether fenbendazole could act as a radiosensitizer in cancer cells by investigating its effects on cell viability in hypoxic cultures of EMT6 human breast carcinoma cells. Hypoxia was achieved by sealing the culture bottles in rubber gaskets, allowing for the influx and efflux of oxygen with needles placed at the septum, and incubating under hypoxic conditions (1 ppm oxygen).

The effect of FZ on microtubule polymerization was studied in A549 human NSCLC cells treated with different microtubule targeting agents and analyzed by immunofluorescence using anti-a-tubulin antibody (6-11B-1). While nocodazole, colchicine and taxol caused depolymerization of tubulin, treatment of cells with FZ had only a mild effect on the stabilization of microtubules. In addition, a fluorescence based competitive colchicine binding assay showed that FZ bound to the tubulin at the colchicine binding site but not to any of the other tested compounds (Fig. S1).

Because fenbendazole is known to block cell-cycle progression and to induce mitotic catastrophe, the effect of FZ on cyclin B1 acetylation in human NSCLC cells was investigated. A549 cells were serum starved for 48 h and treated with 1 uM FZ. The cell cycle was monitored by analyzing the accumulation of a luciferase reporter gene-linked cyclin B1 in culture supernatants at the indicated time points.

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