Antitumor Effects of a New Retinoate of the Fungal Cytotoxin Illudin M in Brain Tumor Models

Linder, Benedikt and Zoldakova, Miroslava and Környei, Zsuzsanna and Köhler, Leonhard H. F. and Seibt, Sebastian and Madarász, Emilia (2022) Antitumor Effects of a New Retinoate of the Fungal Cytotoxin Illudin M in Brain Tumor Models. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23 (16). ISSN 1661-6596

Preview

Text AntitumorEffectsofaNewRetinoate....pdf Available under License Creative Commons Attribution. Download (6MB) | Preview

Abstract

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.

Actions (login required)

Edit Item