In a series of studies in human and mouse cancer cells, the antihelmintic drug fenbendazole has been found to have cytotoxic and radiosensitizing properties. It is also a promising candidate for combination therapy with hypoxia-selective nitroheterocyclic chemotherapeutic agents such as the taxanes. To better understand the pharmacological effects of fenbendazole, we have conducted qualitative and quantitative analytical analysis of a commercially available formulation, which is marketed under the brand names Brand P (panacur(r) C) and Brand S (safe-guard(r) 4).
EMT6 mammary tumor cells were treated with graded doses of fenbendazole for 2 or 24 h in a standard colony formation assay. The results show that fenbendazole reduced both the number of cells in cultures and their clonogenicity, but did not affect cell viability. The cytotoxic effects of fenbendazole were enhanced by exposure to severe hypoxia, as demonstrated by the yield-corrected surviving fractions, which are corrected for differences in the numbers of colonies formed in control cultures.
Several experiments were performed to investigate the in vivo effects of fenbendazole on EMT6 tumors growing in BALB/cRw mice. Tumor volume was measured in untreated and irradiated mice and in mice receiving three daily i.p. injections of fenbendazole with and without 10 Gy of x-rays. Treatment with fenbendazole did not alter tumor growth, but did significantly increase the sensitivity of tumors to radiation.
Quantitative HPLC and LC-MS analyses confirmed that the quantity of fenbendazole measured agreed with the quantities specified on each product label. Qualitative NMR experiments showed that fenbendazole is soluble in dimethyl sulfoxide and that both brands of fenbendazole contain this active ingredient, although they also contained other ingredients not mentioned on the products’ labels. Using this information, we developed and validated a quick, simple, robust and cost-effective method for measuring the concentration of fenbendazole in samples taken from each of the two fenbendazole powders at different time points. fenbendazole for cancer