Despite all the progress in cancer treatment, glioblastoma remains a terminal disease and new therapeutic approaches are urgently needed. Base on previous research, Cathepsin L inhibition was suggested as one of therapeutic modifications but the mechanism of cathepsin L anti-apoptotic activity is largely unknown. In this study we showed that in U87 glioblastoma cells cathepsin L can be present in the nucleus and regulates the transcription of effector caspases 3 and 7. We pointed out on the importance of protein p53 in this process and since p53 pathways are often mutated in glioblastoma, the findings of our study are important to consider before using cathepsin L inhibition for glioblastoma therapy and suggested that such adjuvant therapy may be efficient for only in p53 wild type subpopulation of glioblastoma patients.
This article describes resveratrol, a phytoalexin abundantly present in a variety of diet productsthat has been reported to elicit many cellular responses, including cell cycle arrest, apoptosis and senescence. Cultured human U87MG cells and primary human glioblastoma cultures were used to demonstrate the effects of chronically administered resveratrol, eliciting not only cell growth arrest and cell toxicity, but also limiting cell migration and invasion and promoting long-lasting morphological changes reminiscent of a more mature phenotype. In the cells that survived chronic administration of resveratrol, the expression of differentiation markers of mature glial cells and of neurons, was increased, lasting long up to 96 h after resveratrol was removed. The present findings support the introduction of pulsed administration of resveratrol in the chemotherapy regimen of glioma
CD133 is a marker for a population of glioblastoma (GBM) and normal neural stem cells (NNSC). We aimed to reveal whether the migratory potential and differentiation of these stem cells is associated with CD133 expression and with cathepsin proteases (Cats). The study confirms CD133 as a prognostic marker for the survival of GBM patients. We demonstrated that normal neural stem cells as well as differentiated malignant GBM cells have higher invasion potential and invade the collagen matrix in a mode different from that of CD133+ GBM stem cell spheres. These results could have implications for the design of new therapeutics, including protease inhibitors.