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. 2013 Feb;33(2):355-62.

Fenbendazole as a potential anticancer drug

Qiwen Duan  1 , Yanfeng Liu, Sara Rockwell
Affiliations

Fenbendazole as a potential anticancer drug

Qiwen Duan et al. Anticancer Res. 2013 Feb.

Abstract

Background/aims: To evaluate the anticancer activity of fenbendazole, a widely used antihelminth with mechanisms of action that overlap with those of the hypoxia-selective nitroheterocyclic cytotoxins/radiosensitizers and the taxanes.

Materials and methods: We used EMT6 mouse mammary tumor cells in cell culture and as solid tumors in mice to examine the cytotoxic and antitumor effects of fenbendazole as a single agent and in combination regimens.

Results: Intensive treatments with fenbendazole were toxic to EMT6 cells in vitro; toxicity increased with incubation time and under conditions of severe hypoxia. Fenbendazole did not alter the dose-response curves for radiation or docetaxel; instead, the agents produced additive cytotoxicities. Febendazole in maximally-intensive regimens did not alter the growth of EMT6 tumors, or increase the antineoplastic effects of radiation.

Conclusion: These studies provided no evidence that fenbendazole would have value in cancer therapy, but suggested that this general class of compounds merits further investigation.

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Figures

Figure 1
Figure 1
Effect of graded doses of fenbendazole on the viability of exponentially growing EMT6 cells in cell culture. A: Survival of cells treated with fenbendazole for 2 or 24 h, then assayed for cell survival using a colony formation assay. Survivals are shown both as surviving fractions and as yield-corrected surviving fractions (YCSF), which are corrected for differences in cell number in treated and control cultures at the end of treatment. B: Effect of severe hypoxia on the survival of cells treated for 2 h with fenbendazole. Points are geometric means±SEM of data from three independent experiments.
Figure 2
Figure 2
Effect of treatment with 10 μM fenbendazole on the radiation response of EMT6 cells in vitro. Cultures were treated with graded doses of radiation under aerobic or hypoxic conditions and assayed for cell survival using a colony formation assay. Points are geometric means±SEM of data from three independent experiments.
Figure 3
Figure 3
Effect of three i.p. injections of Fenbendazole on the growth and radiation response of EMT6 tumors in BALB/cRw mice. Tumor-bearing mice were randomized at a mean tumor volume of 100 mm3 to serve as untreated controls, to receive three daily i.p. injections with 50/mg/kg/day fenbendazole at the times shown by the three dark arrows, to receive 10 Gy of x-rays given at the time indicated by the large open arrow, or to receive Fenbendazole plus x-rays. Points are geometric means±SEM; 7–8 mice/group. Further analyses of these data are shown in Table I.
Figure 4
Figure 4
Effect of 10 μM fenbendazole on the response of EMT6 cells to graded doses of docetaxel. Fenbendazole was added to the cultures either a few seconds or 22 h before the start of a 2-h treatment with graded doses of docetaxel. Relative surviving fractions were calculated using either the untreated control cultures (for docetaxel alone) or the corresponding Fenbendazole-treated cultures (for fenbendazole + docetaxel) from the same experiments. Points are geometric means±SEM from three independent experiments.
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References

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