>>AUSTIN, Texas, Oct. 17 /PRNewswire-FirstCall/ -- A preclinical study published in the journal 'Clinical Cancer Research' demonstrates the potent activity of a new class of anti-cancer agents. Introgen Therapeutics, Inc. (Nasdaq: INGN - News) and its collaborators at M.D. Anderson have discovered that Mebendazole, a drug widely used to treat parasitic infections, shows remarkable activity against human lung cancer cells. The study shows that Mebendazole potently kills malignant human lung cancer cells, without toxicity to normal cells. Moreover, when administered to mice bearing human lung tumors, Mebendazole strongly inhibited the growth of the tumors, and significantly reduced their number and size. Introgen has acquired worldwide rights to the new application of Mebendazole, which is in preclinical stages of development.
"This is the first report of Mebendazole's anti-cancer activity both in vitro and in vivo, and it appears this activity is potent and broadly applicable to a variety of cancer cell types. If this anti-cancer activity is accompanied by diminished toxicity, as suggested in this study, and by human experience with the drug, cancer patients could benefit substantially from this therapy," said Sunil Chada, Ph.D. Introgen's director of research and development.
The study, authored by Tapas Mukhopadhyay, Ph.D., assistant professor in the department of thoracic and cardiovascular surgery at M. D. Anderson, also evaluated the mechanism of activity of Mebendazole. As expected from its ability to bind tubulin, Mebendazole treatment of tumor cells resulted in cell cycle arrest. The researchers then found that the cells underwent programmed cell death (apoptosis) after cell cycle arrest. They also discovered that Mebendazole is a potent inhibitor of angiogenesis, and Mebendazole treatment resulted in inhibition of growth of new blood vessels that feed tumors. When tested against human lung tumors growing in mice, Mebendazole reduced tumor growth by more than 80 percent compared to untreated tumors. In models of metastatic lung cancer, Mebendazole treatment reduced the number of lung metastases by 80 percent, thus, Mebendazole may have substantial utility in treating cancer.
"Mebendazole appears to be a prototype for a new class of anti-cancer drugs which display tumor-specificity coupled with low toxicity. We are very encouraged that this drug, which has been used to treat parasitic infections for almost 20 years and has a long record of safe clinical use, shows such potent activity against cancer cells. These studies serve as a solid foundation to evaluate this drug as a new treatment for cancer patients," said Jack A. Roth, M.D., chairman of the department of thoracic and cardiovascular surgery at M. D. Anderson and a co-author of the paper. Dr. Roth also serves as a scientific advisor to Introgen and is chairman of its scientific advisory board.
Mebendazole, a drug long used for the oral treatment of parasitic diseases, was not previously known to have anti-cancer activity. However, earlier studies had shown that Mebendazole could disrupt microtubule dynamics, which can arrest the cell cycle, placing it in a similar functional class as the taxanes, a group of drugs that have anti-tumor activity against a range of cancers. Experience with Mebendazole in animal models and in humans has not shown the significant toxicities associated with the taxanes, suggesting that Mebendazole may have a novel mechanism of action, and could ultimately prove to be a safer chemotherapy.<<
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>>Clin Cancer Res 2002 Sep;8(9):2963-9
Mebendazole elicits a potent antitumor effect on human cancer cell lines both in vitro and in vivo.
Mukhopadhyay T, Sasaki J, Ramesh R, Roth JA.
Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030.
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.<<
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