The Anthelmintic Drug Mebendazole Induces Mitotic Arrest and Apoptosis by Depolymerizing Tubulin in Non-Small Cell Lung Cancer Cells 1 Supported in part by grants from the National Cancer Institute and the NIH Specialized Program of Research Excellence in Lung Cancer P-50-CA70907 and P01 CA78778-01A1 (both to J. A. R.), by gifts to the Division of Surgery and Anesthesiology from Tenneco and Exxon for the Core Laboratory Facility, by The University of Texas M. D. Anderson Cancer Center Support Co

• Published in: Molecular cancer therapeutics Vol. 1; no. 13; p. 1201
• Main Authors: Ji-ichiro Sasaki, Rajagopal Ramesh, Sunil Chada, Yoshihito Gomyo, Jack A. Roth, Tapas Mukhopadhyay
• Format: Journal Article
• Language: English
• Published: American Association for Cancer Research 01-11-2002
• ISSN: 1535-7163; 1538-8514

Microtubules have a critical role in cell division, and consequently various microtubule inhibitors have been developed as
anticancer drugs. In this study, we assess mebendazole (MZ), a microtubule-disrupting anthelmintic that exhibits a potent
antitumor property both in vitro and in vivo . Treatment of lung cancer cell lines with MZ caused mitotic arrest, followed by apoptotic cell death with the feature of
caspase activation and cytochrome c release. MZ induces abnormal spindle formation in mitotic cancer cells and enhances the depolymerization of tubulin, but
the efficacy of depolymerization by MZ is lower than that by nocodazole. Oral administration of MZ in mice elicited a strong
antitumor effect in a s.c. model and reduced lung colonies in experimentally induced lung metastasis without any toxicity
when compared with paclitaxel-treated mice. We speculate that tumor cells may be defective in one mitotic checkpoint function
and sensitive to the spindle inhibitor MZ. Abnormal spindle formation may be the key factor determining whether a cell undergoes
apoptosis, whereas strong microtubule inhibitors elicit toxicity even in normal cells.