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Cold Atmospheric Plasma Increases Temozolomide Sensitivity of Three-Dimensional Glioblastoma Spheroids via Oxidative Stress-Mediated DNA Damage.
Shaw, Priyanka; Kumar, Naresh; Privat-Maldonado, Angela; Smits, Evelien; Bogaerts, Annemie.
Afiliación
  • Shaw P; Research Group PLASMANT, Department of Chemistry, University of Antwerp, 2610 Antwerp, Belgium.
  • Kumar N; Solid Tumor Immunology Group, Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, 2610 Antwerp, Belgium.
  • Privat-Maldonado A; Research Group PLASMANT, Department of Chemistry, University of Antwerp, 2610 Antwerp, Belgium.
  • Smits E; National Institute of Pharmaceutical Education and Research, Guwahati, Guwahati 781125, Assam, India.
  • Bogaerts A; Research Group PLASMANT, Department of Chemistry, University of Antwerp, 2610 Antwerp, Belgium.
Cancers (Basel) ; 13(8)2021 Apr 08.
Article en En | MEDLINE | ID: mdl-33917880
Glioblastoma multiforme (GBM) is the most frequent and aggressive primary malignant brain tumor in adults. Current standard radiotherapy and adjuvant chemotherapy with the alkylating agent temozolomide (TMZ) yield poor clinical outcome. This is due to the stem-like properties of tumor cells and genetic abnormalities in GBM, which contribute to resistance to TMZ and progression. In this study, we used cold atmospheric plasma (CAP) to enhance the sensitivity to TMZ through inhibition of antioxidant signaling (linked to TMZ resistance). We demonstrate that CAP indeed enhances the cytotoxicity of TMZ by targeting the antioxidant specific glutathione (GSH)/glutathione peroxidase 4 (GPX4) signaling. We optimized the threshold concentration of TMZ on five different GBM cell lines (U251, LN18, LN229, U87-MG and T98G). We combined TMZ with CAP and tested it on both TMZ-sensitive (U251, LN18 and LN229) and TMZ-resistant (U87-MG and T98G) cell lines using two-dimensional cell cultures. Subsequently, we used a three-dimensional spheroid model for the U251 (TMZ-sensitive) and U87-MG and T98G (TMZ-resistant) cells. The sensitivity of TMZ was enhanced, i.e., higher cytotoxicity and spheroid shrinkage was obtained when TMZ and CAP were administered together. We attribute the anticancer properties to the release of intracellular reactive oxygen species, through inhibiting the GSH/GPX4 antioxidant machinery, which can lead to DNA damage. Overall, our findings suggest that the combination of CAP with TMZ is a promising combination therapy to enhance the efficacy of TMZ towards the treatment of GBM spheroids.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Diagnostic_studies / Prognostic_studies Idioma: En Revista: Cancers (Basel) Año: 2021 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Diagnostic_studies / Prognostic_studies Idioma: En Revista: Cancers (Basel) Año: 2021 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Suiza