Fenben lab fenbendazol is one of the three broad-spectrum benzimidazole carbamate anthelmintics that have been in use as anthelmintics for about six decades. These drugs are relatively safe and effective against most roundworm species. Benzimidazoles also have antitumor activity in mice and other animals [1]. Fenbendazole inhibits polymerization of tubulin, which makes up microtubules that form part of the cytoskeleton that provides structure and shape to cells. Microtubules play a critical role in cell division and are targeted by some cytotoxic anticancer agents, such as vinca alkaloids [2].
In this preclinical study, nude mice bearing tumors of human nonsmall-cell lung cancer received 1 mg/kg oral fenbendazole daily for 12 days. Tumors were irradiated locally with 10 Gy of 250 kV X-rays using a Siemens Stabilipan (Malvern, PA). Fenbendazole treatment significantly decreased tumor size and vascularity in the lungs. Treatment also caused a significant reduction in tumor progression to metaphase in the A549 cell line. This effect was attributed to inhibition of microtubules by fenbendazole, which prevented binding of cyclin B1 to cyclin-dependent kinase 1, thereby blocking mitotic catastrophe.
In addition, the number of neutrophils in the lungs was significantly reduced after fenbendazole treatment. This reduction in neutrophils was attributed to diminished tumor compression and necrosis of adjacent tissues. Vitamin concentrations in the prepared diet used during this study deteriorated with time, however, so it is possible that the initial inhibition observed was a result of lessened vitamin concentrations. These results suggest that fenbendazole might be a promising candidate for human therapy.
No comments:
Post a Comment