Antitumor Effects of a New Retinoate of the Fungal Cytotoxin Illudin M in Brain Tumor Models
Autor: | Benedikt Linder, Miroslava Zoldakova, Zsuzsanna Kornyei, Leonhard H. F. Köhler, Sebastian Seibt, Dominic Menger, André Wetzel, Emília Madarász, Rainer Schobert, Donat Kögel, Bernhard Biersack |
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Rok vydání: | 2022 |
Předmět: |
Polycyclic Sesquiterpenes
Brain Neoplasms Cytotoxins Organic Chemistry Tretinoin General Medicine Glioma Catalysis Computer Science Applications Inorganic Chemistry Astrocytes Glial Fibrillary Acidic Protein Humans illudin M retinoic acid neuronal cells brain tumors anticancer agents Physical and Theoretical Chemistry Molecular Biology Spectroscopy |
Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 16; Pages: 9056 |
ISSN: | 1422-0067 |
Popis: | 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. |
Databáze: | OpenAIRE |
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