A whole-genome scan for Artemisinin cytotoxicity reveals a novel therapy for human brain tumors.

ABSTRACT: The natural compound Artemisinin is the most widely used antimalarial drug worldwide. Based on its cytotoxicity, it is also used for anticancer therapy. Artemisinin and its derivates are endoperoxides that damage proteins in eukaryotic cells; their definite mechanism of action and host cell targets, however, have remained largely elusive. Using yeast and haploid stem cell screening, we demonstrate that a single cellular pathway, namely porphyrin (heme) biosynthesis, is required for the cytotoxicity of Artemisinins. Genetic or pharmacological modulation of porphyrin production is sufficient to alter its cytotoxicity in eukaryotic cells. Using multiple model systems of human brain tumor development, such as cerebral glioblastoma organoids, and patient-derived tumor spheroids, we sensitize ca

SUBMITTER: Taubenschmid-Stowers J 

PROVIDER: S-EPMC10237280 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature