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Article

Effects of the Anti-Tumorigenic Agent AT101 on Human Glioblastoma Cells in the Microenvironmental Glioma Stem Cell Niche

Department of Neurosurgery, University Medical Center Schleswig-Holstein UKSH, Campus Kiel, 24105 Kiel, Germany
*
Author to whom correspondence should be addressed.
Shared first authorship.
Academic Editor: Silvia Deaglio
Int. J. Mol. Sci. 2021, 22(7), 3606; https://doi.org/10.3390/ijms22073606
Received: 19 February 2021 / Revised: 23 March 2021 / Accepted: 27 March 2021 / Published: 30 March 2021
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. View Full-Text
Keywords: tumor stem-like cells; microenvironment; heterogeneity; chemoresistance; R-(-)-gossypol; temozolomide; glioblastoma; CXCR7; IL-6R tumor stem-like cells; microenvironment; heterogeneity; chemoresistance; R-(-)-gossypol; temozolomide; glioblastoma; CXCR7; IL-6R
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MDPI and ACS Style

Caylioglu, D.; Meyer, R.J.; Hellmold, D.; Kubelt, C.; Synowitz, M.; Held-Feindt, J. Effects of the Anti-Tumorigenic Agent AT101 on Human Glioblastoma Cells in the Microenvironmental Glioma Stem Cell Niche. Int. J. Mol. Sci. 2021, 22, 3606. https://doi.org/10.3390/ijms22073606

AMA Style

Caylioglu D, Meyer RJ, Hellmold D, Kubelt C, Synowitz M, Held-Feindt J. Effects of the Anti-Tumorigenic Agent AT101 on Human Glioblastoma Cells in the Microenvironmental Glioma Stem Cell Niche. International Journal of Molecular Sciences. 2021; 22(7):3606. https://doi.org/10.3390/ijms22073606

Chicago/Turabian Style

Caylioglu, Deniz, Rieke J. Meyer, Dana Hellmold, Carolin Kubelt, Michael Synowitz, and Janka Held-Feindt. 2021. "Effects of the Anti-Tumorigenic Agent AT101 on Human Glioblastoma Cells in the Microenvironmental Glioma Stem Cell Niche" International Journal of Molecular Sciences 22, no. 7: 3606. https://doi.org/10.3390/ijms22073606

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