Effects of the Anti-Tumorigenic Agent AT101 on Human Glioblastoma Cells in the Microenvironmental Glioma Stem Cell Niche
Autor: | Dana Hellmold, Deniz Caylioglu, Carolin Kubelt, Rieke Meyer, Michael Synowitz, Janka Held-Feindt |
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Rok vydání: | 2021 |
Předmět: |
Carcinogenesis
temozolomide Biology IL-6R Catalysis Article Inorganic Chemistry lcsh:Chemistry Glioma Cell Line Tumor R-(-)-gossypol Antineoplastic Combined Chemotherapy Protocols medicine Tumor Microenvironment Cytotoxic T cell Humans Physical and Theoretical Chemistry Stem Cell Niche Receptor Molecular Biology lcsh:QH301-705.5 tumor stem-like cells Spectroscopy Cell Proliferation Temozolomide Brain Neoplasms Organic Chemistry Gossypol glioblastoma Brain chemoresistance General Medicine medicine.disease microenvironment CXCR7 Stem cell niche Computer Science Applications lcsh:Biology (General) lcsh:QD1-999 Cell culture Drug Resistance Neoplasm Cancer research Neoplastic Stem Cells Signal transduction heterogeneity Glioblastoma medicine.drug Signal Transduction |
Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 3606, p 3606 (2021) Volume 22 Issue 7 |
ISSN: | 1422-0067 |
Popis: | Glioblastoma (GBM) is a barely treatable disease due to its profound chemoresistance. A distinct inter- and intratumoral heterogeneity reflected by specialized microenvironmental niches and different tumor cell subpopulations allows GBMs to evade therapy regimens. Thus, there is an urgent need to develop alternative treatment strategies. A promising candidate for the treatment of GBMs is AT101, the R(-) enantiomer of gossypol. The present study evaluates the effects of AT101, alone or in combination with temozolomide (TMZ), in a microenvironmental glioma stem cell niche model of two GBM cell lines (U251MG and U87MG). AT101 was found to induce strong cytotoxic effects on U251MG and U87MG stem-like cells in comparison to the respective native cells. Moreover, a higher sensitivity against treatment with AT101 was observed upon incubation of native cells with a stem-like cell-conditioned medium. This higher sensitivity was reflected by a specific inhibitory influence on the p-p42/44 signaling pathway. Further, the expression of CXCR7 and the interleukin-6 receptor was significantly regulated upon these stimulatory conditions. Since tumor stem-like cells are known to mediate the development of tumor recurrences and were observed to strongly respond to the AT101 treatment, this might represent a promising approach to prevent the development of GBM recurrences. |
Databáze: | OpenAIRE |
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