The mycotoxin viriditoxin induces leukemia- and lymphoma-specific apoptosis by targeting mitochondrial metabolism

• DOI: 10.1038/s41419-022-05356-w
• Publication Date: 2022-11-08T08:03:20Z
• Authors: Fabian Stuhldreier; Laura Schmitt; Thomas Lenz; Ilka Hinxlage; Marcel Zimmermann; Philipp Wollnitzke; Julian Schliehe-D...; Yang Liu; Paul Jäger; Stefanie Geyh; Nicole Teusch; Christoph Peter; Sanil Bhatia; Rainer Haas; Bodo Levkau; Andreas S. Reichert; Kai Stühler; Peter Proksch; Björn Stork; Sebastian Wesselborg
• Keywords: Membrane Potential, Mitochondrial; 0301 basic medicine; Leukemia; QH573-671; Lymphoma; Apoptosis; Mycotoxins; Article; Mitochondria; 3. Good health; 03 medical and health sciences; Leukocytes, Mononuclear; Humans; Cytology; Reactive Oxygen Species

Abstract Inhibition of the mitochondrial metabolism offers a promising therapeutic approach for treatment cancer. Here, we identify mycotoxin viriditoxin (VDT), derived from endophytic fungus Cladosporium cladosporioides , as an interesting candidate leukemia and lymphoma treatment. VDT displayed high cytotoxic potential rapid kinetics caspase activation in Jurkat Ramos cells contrast to solid tumor that were affected much lesser extent. Most remarkably, human hematopoietic stem progenitor peripheral blood mononuclear healthy donors profoundly resilient VDT-induced cytotoxicity. Likewise, colony-forming capacity was only at very concentrations, which provides window cancer Intriguingly, could directly activate apoptosis pathway presence antiapoptotic Bcl-2 proteins. The toxicity further confirmed by inhibition respiration, breakdown membrane (ΔΨm), release cytochrome c, generation reactive oxygen species (ROS), processing dynamin-like GTPase OPA1 subsequent fission mitochondria. Thus, VDT-mediated targeting oxidative phosphorylation (OXPHOS) might represent without affecting cells.