Glioblastoma (GBM) is the most common astrocytic-derived brain tumor in adults, characterized by a poor prognosis mainly due to the resistance to the available therapy. The study of mitochondria-derived oxidative stress, and of the biological events that orbit around it, might help in the comprehension of the molecular mechanisms at the base of GBM responsiveness to Temozolomide (TMZ). Sensitive and resistant GBM cells were used to test the role of mitochondrial ROS release in TMZ-resistance. Chaperone-Mediated Autophagy (CMA) activation in relation to reactive oxygen species (ROS) release has been measured by monitoring the expression of specific genes. Treatments with H2O2 were used to test their potential in reverting resistance. Fluctuations of cytoplasmic ROS levels were accountable for CMA induction and cytotoxic effects observed in TMZ sensitive cells after treatment. On the other hand, in resistant cells, TMZ failed in producing an increase in cytoplasmic ROS levels and CMA activation, preventing GBM cell toxicity. By increasing oxidative stress, CMA activation was recovered, as also cell cytotoxicity, especially in combination with TMZ treatment. Herein, for the first time, it is shown the relation between mitochondrial ROS release, CMA activation and TMZ-responsiveness in GBM.
Intracellular Redox-Balance Involvement in Temozolomide Resistance-Related Molecular Mechanisms in Glioblastoma / A. Lo Dico, D. Salvatore, C. Martelli, D. Ronchi, C. Diceglie, G. Lucignani, L. Ottobrini. - In: CELLS. - ISSN 2073-4409. - 8:11(2019 Oct 24), pp. 1315.1-1315.17.
|Titolo:||Intracellular Redox-Balance Involvement in Temozolomide Resistance-Related Molecular Mechanisms in Glioblastoma|
OTTOBRINI, LUISA (Corresponding)
|Parole Chiave:||chaperone mediated autophagy (CMA); drug resistance; mitochondrial scavenger; oxidative stress; reactive oxygen species (ROS), cell motility|
|Settore Scientifico Disciplinare:||Settore MED/50 - Scienze Tecniche Mediche Applicate|
|Progetto:||Development of an integrated SPECT/MRI system for enhanced stratification of brain tumour patients prior to patient-specific radio-chemo therapy and early assessment of treatment efficacy|
|Data di pubblicazione:||24-ott-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3390/cells8111315|
|Appare nelle tipologie:||01 - Articolo su periodico|
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