Glioblastoma multiforme (GBM) belongs to most aggressive and invasive primary brain tumor in adults whose prognosis and survival remains poor. Potential new treatment modalities include targeting the cytoskeleton. In our study, we demonstrated that repurposed drug flubendazole (FLU) significantly inhibits proliferation and survival of GBM cells. FLU exerted its effect by affecting microtubule structure and our results also suggest that FLU influences tubulins expression to a certain degree. Moreover, FLU effects decreased activation of STAT3 and also partially inhibited its expression, leading to upregulation of p53 signaling pathway and subsequent cell cycle arrest at G2/M phase as well as caspase-dependent cell death in GBM cells. These results suggest FLU as a promising agent to be used in GBM treatment and prompting further testing of its effects on GBM.

• MeSH
• Apoptosis MeSH
• Cell Cycle MeSH
• Adult MeSH
• Glioblastoma * pathology   MeSH
• Cell Cycle Checkpoints MeSH
• Humans MeSH
• Mebendazole pharmacology   therapeutic use   MeSH
• Cell Line, Tumor MeSH
• Brain Neoplasms * pathology   MeSH
• Cell Proliferation MeSH
• STAT3 Transcription Factor metabolism   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• flubendazole MeSH Browser
• Mebendazole MeSH
• STAT3 protein, human MeSH Browser
• STAT3 Transcription Factor MeSH

Glioblastoma multiforme (GBM) represents approximately 60% of all brain tumors in adults. This malignancy shows a high biological and genetic heterogeneity associated with exceptional aggressiveness, leading to a poor survival of patients. This review provides a summary of the basic biology of GBM cells with emphasis on cell cycle and cytoskeletal apparatus of these cells, in particular microtubules. Their involvement in the important oncosuppressive process called mitotic catastrophe will next be discussed along with select examples of microtubule-targeting agents, which are currently explored in this respect such as benzimidazole carbamate compounds. Select microtubule-targeting agents, in particular benzimidazole carbamates, induce G2/M cell cycle arrest and mitotic catastrophe in tumor cells including GBM, resulting in phenotypically variable cell fates such as mitotic death or mitotic slippage with subsequent cell demise or permanent arrest leading to senescence. Their effect is coupled with low toxicity in normal cells and not developed chemoresistance. Given the lack of efficient cytostatics or modern molecular target-specific compounds in the treatment of GBM, drugs inducing mitotic catastrophe might offer a new, efficient alternative to the existing clinical management of this at present incurable malignancy.

• Keywords
• benzimidazole carbamates, cell death, glioblastoma multiforme, microtubule-targeting agents, mitotic catastrophe,
• MeSH
• Glioblastoma * metabolism   mortality   therapy   MeSH
• G2 Phase Cell Cycle Checkpoints * MeSH
• M Phase Cell Cycle Checkpoints * MeSH
• Humans MeSH
• Mitosis * MeSH
• Brain Neoplasms * metabolism   mortality   pathology   therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH