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

Author:

Linder BenediktORCID,Zoldakova Miroslava,Kornyei ZsuzsannaORCID,Köhler Leonhard H. F.,Seibt Sebastian,Menger DominicORCID,Wetzel André,Madarász EmíliaORCID,Schobert RainerORCID,Kögel DonatORCID,Biersack BernhardORCID

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.

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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