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Study of the Effect of Flubendazole on the Glioblastoma Multiforme Cells In Vitro and In Vivo
Vítovcová, Barbora ; Rudolf, Emil (advisor) ; Slaninová, Iva (referee) ; Jendelová, Pavla (referee)
Study of the effect of flubendazole on the glioblastoma multiforme cells in vitro and in vivo Glioblastoma multiforme (GBM) belongs to one of the most common and most aggressive primary brain tumours in adults. Current therapeutic strategy is insufficient, and patient's prognosis is unfavourable, therefore prompting an intensive effort to improve therapeutic options of GBM. Present research focuses mainly on the identification of the new possible targets for therapy or on the optimalization of already existing treatment strategies in GBM. Highly discussed approach to GBM therapy is microtubule targeting, which is one of the fundamental ways to tumour treatment. For this purpose, chemotherapeutics already in current common practice or drugs originally intended for a different indication, such as flubendazole (FLU), originally human and veterinary anthelmintic, could be used. In previous studies FLU has already demonstrated an inhibitory effect on cells of various solid tumours and haematological malignancies through a specific interaction with microtubules. The aim of this work was to evaluate the inhibitory effect of FLU in different in vitro and in vivo GBM models. Study of FLU effect was performed in vitro using stabilized GBM cell lines (A172, T98G and U118MG) and GBM primary cultures derived from...
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Analysis of Growth-inhibitory Mechanism of Flubendazole in Malignant Melanoma Cells
Čáňová, Kristýna ; Rudolf, Emil (advisor) ; Slaninová, Iva (referee) ; Mandys, Václav (referee)
Analysis of growth-inhibitory mechanisms of flubendazole in malignant melanoma cells Malignant skin melanoma is at its advanced stage highly aggressive and chemoresistant to almost all currently available therapies. Moderns efforts are thus aimed to identify new targets in melanoma cells or to take advantage of novel indications of already approved drugs - a process called drug repurposing. This work was focused on evaluation of cell growth inhibitory properties of one such drug - flubendazole (FLU) - a widely used anthelmintic compound belonging to benzimidazole family. This drug specifically interacts with β-tubulin, which results in disruption of microtubule structure and function in the exposed cells. Several members of the benzimidazole family (including FLU) have already shown the growth inhibitory potential in tumor cells derived from breast, colon, blood and nervous system malignancies. Still, the specific activity of FLU in malignant melanoma has not been tested to the date. Cytotoxicity of FLU was tested in three malignant melanoma cell lines representing diverse melanoma molecular types (A-375, BOWES and RPMI-7951) during up to 72 hours using WST-1 and x-CELLigence assays. Based on achieved IC50 from individual cell lines, the 1 µM FLU concentration was selected for further testing. While...
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