| Autor: |
Linder B; Experimental Neurosurgery, Frankfurt University Hospital, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany., Zoldakova M; Organic Chemistry 1, University of Bayreuth, Universitätsstrasse 30, 95440 Bayreuth, Germany., Kornyei Z; Laboratory of Cellular and Developmental Neurobiology, Institute of Experimental Medicine of the Hungarian Academy of Sciences, Szigony utca 43, HU-1083 Budapest, Hungary., Köhler LHF; Organic Chemistry 1, University of Bayreuth, Universitätsstrasse 30, 95440 Bayreuth, Germany., Seibt S; Organic Chemistry 1, University of Bayreuth, Universitätsstrasse 30, 95440 Bayreuth, Germany., Menger D; Experimental Neurosurgery, Frankfurt University Hospital, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany., Wetzel A; Organic Chemistry 1, University of Bayreuth, Universitätsstrasse 30, 95440 Bayreuth, Germany., Madarász E; Laboratory of Cellular and Developmental Neurobiology, Institute of Experimental Medicine of the Hungarian Academy of Sciences, Szigony utca 43, HU-1083 Budapest, Hungary., Schobert R; Organic Chemistry 1, University of Bayreuth, Universitätsstrasse 30, 95440 Bayreuth, Germany., Kögel D; Experimental Neurosurgery, Frankfurt University Hospital, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany., Biersack B; Organic Chemistry 1, University of Bayreuth, Universitätsstrasse 30, 95440 Bayreuth, Germany. |
| Abstrakt: |
While the fungal metabolite illudin M ( 1 ) is indiscriminately cytotoxic in cancer and non-malignant cells, its retinoate 2 showed a greater selectivity for the former, especially in a cerebral context. Illudin M killed malignant glioma cells as well as primary neurons and astrocytes at similarly low concentrations and destroyed their microtubule and glial fibrillary acidic protein (GFAP) networks. In contrast, the ester 2 was distinctly more cytotoxic in highly dedifferentiated U87 glioma cells than in neurons, which were even stimulated to enhanced growth. This was also observed in co-cultures of neurons with U87 cells where conjugate 2 eventually killed them by induction of differentiation based on the activation of nuclear receptors, which bind to retinoid-responsive elements (RARE). Hence, illudin M retinoate 2 appears to be a promising drug candidate. |
