Mebendazole Elicits a Potent Antitumor Effect on Human

We have found that mebendazole (MZ), a derivative of benzimidazole, induces a doseand time-dependent apoptotic response in human lung cancer cell lines. In this study, MZ arrested cells at the G2-M phase before the onset of apoptosis, as detected by using fluorescence-activated cell sorter analysis. MZ treatment also resulted in mitochondrial cytochrome c release, followed by apoptotic cell death. Additionally, MZ appeared to be a potent inhibitor of tumor cell growth with little toxicity to normal WI38 and human umbilical vein endothelial cells. When administered p.o. to nu/nu mice, MZ strongly inhibited the growth of human tumor xenografts and significantly reduced the number and size of tumors in an experimental model of lung metastasis. In assessing angiogenesis, we found significantly reduced vessel densities in MZ-treated mice compared with those in control mice. These results suggest that MZ is effective in the treatment of cancer and other angiogenesis-dependent diseases.