Mebendazole elicits a potent antitumor effect on human cancer cell lines both in vitro and in vivo.
We have found that mebendazole (MZ), a derivative of benzimidazole, induces a dose- and time-dependent apoptotic response in human lung cancer cell lines. In this study, MZ arrested cells at the G(2)-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.
Mukhopadhyay
Tapas
T
Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. tmukhopa@manderson.org
Sasaki
Ji-ichiro
J
Ramesh
Rajagopal
R
Roth
Jack A
JA
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D008463:Mebendazole / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D011828:Radiation Chimera; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000637:transplantation; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D008463:Mebendazole