Mebendazole Abstracts 1

© 2012

Antiparasitic mebendazole shows survival benefit in 2 preclinical models of glioblastoma multiforme

            (Bai, Staedtke et al. 2011) Download

Glioblastoma multiforme (GBM) is the most common and aggressive brain cancer, and despite treatment advances, patient prognosis remains poor. During routine animal studies, we serendipitously observed that fenbendazole, a benzimidazole antihelminthic used to treat pinworm infection, inhibited brain tumor engraftment. Subsequent in vitro and in vivo experiments with benzimidazoles identified mebendazole as the more promising drug for GBM therapy. In GBM cell lines, mebendazole displayed cytotoxicity, with half-maximal inhibitory concentrations ranging from 0.1 to 0.3 microM. Mebendazole disrupted microtubule formation in GBM cells, and in vitro activity was correlated with reduced tubulin polymerization. Subsequently, we showed that mebendazole significantly extended mean survival up to 63% in syngeneic and xenograft orthotopic mouse glioma models. Mebendazole has been approved by the US Food and Drug Administration for parasitic infections, has a long track-record of safe human use, and was effective in our animal models with doses documented as safe in humans. Our findings indicate that mebendazole is a possible novel anti-brain tumor therapeutic that could be further tested in clinical trials.

Mebendazole monotherapy and long-term disease control in metastatic adrenocortical carcinoma

            (Dobrosotskaya, Hammer et al. 2011) Download

OBJECTIVE: To describe successful long-term tumor control in metastatic adrenocortical carcinoma, a relatively rare tumor with limited treatment options outside of surgery. METHODS: We present the clinical, radiologic, and pathologic findings in a patient with failure of or intolerance to conventional treatments for metastatic adrenocortical carcinoma. RESULTS: A 48-year-old man with adrenocortical carcinoma had disease progression with systemic therapies including mitotane, 5-fluorouracil, streptozotocin, bevacizumab, and external beam radiation therapy. Treatment with all chemotherapeutic drugs was ceased, and he was prescribed mebendazole, 100 mg twice daily, as a single agent. His metastases initially regressed and subsequently remained stable. While receiving mebendazole as a sole treatment for 19 months, his disease remained stable. He did not experience any clinically significant adverse effects, and his quality of life was satisfactory. His disease subsequently progressed after 24 months of mebendazole monotherapy. CONCLUSION: Mebendazole may achieve long-term disease control of metastatic adrenocortical carcinoma. It is well tolerated and the associated adverse effects are minor.

Mebendazole induces apoptosis via Bcl-2 inactivation in chemoresistant melanoma cells

            (Doudican, Rodriguez et al. 2008) Download

Most metastatic melanoma patients fail to respond to available therapy, underscoring the need for novel approaches to identify new effective treatments. In this study, we screened 2,000 compounds from the Spectrum Library at a concentration of 1 micromol/L using two chemoresistant melanoma cell lines (M-14 and SK-Mel-19) and a spontaneously immortalized, nontumorigenic melanocyte cell line (melan-a). We identified 10 compounds that inhibited the growth of the melanoma cells yet were largely nontoxic to melanocytes. Strikingly, 4 of the 10 compounds (mebendazole, albendazole, fenbendazole, and oxybendazole) are benzimidazoles, a class of structurally related, tubulin-disrupting drugs. Mebendazole was prioritized to further characterize its mechanism of melanoma growth inhibition based on its favorable pharmacokinetic profile. Our data reveal that mebendazole inhibits melanoma growth with an average IC(50) of 0.32 micromol/L and preferentially induces apoptosis in melanoma cells compared with melanocytes. The intrinsic apoptotic response is mediated through phosphorylation of Bcl-2, which occurs rapidly after treatment with mebendazole in melanoma cells but not in melanocytes. Phosphorylation of Bcl-2 in melanoma cells prevents its interaction with proapoptotic Bax, thereby promoting apoptosis. We further show that mebendazole-resistant melanocytes can be sensitized through reduction of Bcl-2 protein levels, showing the essential role of Bcl-2 in the cellular response to mebendazole-mediated tubulin disruption. Our results suggest that this screening approach is useful for identifying agents that show promise in the treatment of even chemoresistant melanoma and identifies mebendazole as a potent, melanoma-specific cytotoxic agent.

Mebendazole inhibits growth of human adrenocortical carcinoma cell lines implanted in nude mice

            (Martarelli, Pompei et al. 2008) Download

Adrenocortical carcinoma is a rare tumor of the adrenal gland which requires new therapeutic approaches as its early diagnosis is difficult and prognosis poor despite therapies used. Recently, mebendazole has been proved to be effective against different cancers. The aim of our study was to evaluate whether mebendazole may result therapeutically useful in the treatment of human adrenocortical carcinoma. We analyzed the effect of mebendazole on human adrenocortical carcinoma cells in vitro and after implantation in nude mice. In order to clarify mechanisms of mebendazole action, metastases formation, apoptosis and angiogenesis were also investigated. Mebendazole significantly inhibited cancer cells growth, both in vitro and in vivo, the effects being due to the induction of apoptosis. Moreover, mebendazole inhibited invasion and migration of cancer cells in vitro, and metastases formation in vivo. Overall, these data suggest that treatment with mebendazole, also in combination with standard therapies, could provide a new protocol for the inhibition of adrenocortical carcinoma growth.

Mebendazole elicits a potent antitumor effect on human cancer cell lines both in vitro and in vivo

            (Mukhopadhyay, Sasaki et al. 2002) Download

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.

The anthelmintic drug mebendazole induces mitotic arrest and apoptosis by depolymerizing tubulin in non-small cell lung cancer cells

            (Sasaki, Ramesh et al. 2002) Download

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.


Bai, R. Y., V. Staedtke, et al. (2011). "Antiparasitic mebendazole shows survival benefit in 2 preclinical models of glioblastoma multiforme." Neuro Oncol 13(9): 974-82.

Dobrosotskaya, I. Y., G. D. Hammer, et al. (2011). "Mebendazole monotherapy and long-term disease control in metastatic adrenocortical carcinoma." Endocr Pract 17(3): e59-62.

Doudican, N., A. Rodriguez, et al. (2008). "Mebendazole induces apoptosis via Bcl-2 inactivation in chemoresistant melanoma cells." Mol Cancer Res 6(8): 1308-15.

Martarelli, D., P. Pompei, et al. (2008). "Mebendazole inhibits growth of human adrenocortical carcinoma cell lines implanted in nude mice." Cancer Chemother Pharmacol 61(5): 809-17.

Mukhopadhyay, T., J. Sasaki, et al. (2002). "Mebendazole elicits a potent antitumor effect on human cancer cell lines both in vitro and in vivo." Clin Cancer Res 8(9): 2963-9.

Sasaki, J., R. Ramesh, et al. (2002). "The anthelmintic drug mebendazole induces mitotic arrest and apoptosis by depolymerizing tubulin in non-small cell lung cancer cells." Mol Cancer Ther 1(13): 1201-9.