Dihydroartemisinin induces tumor suppression in the Drosophila brain tumor with functional recovery and a rescue in lethality

With a poor prognosis and dynamic invasiveness, gliomas persist as one of the elusive targets in modern oncology, catalyzing a shift in focus towards natural product-based anti-glioma candidates that prioritize therapeutic precision with minimal toxicity. In a previous study conducted in our laboratory, treatment of the Drosophila brain tumor mutant, lethal (2) giant larvae [l(2)gl] with candidate drugs artemisinin and curcumin restored brain architecture, though pupal lethality persisted. Here, we investigate a key artemisinin derivative, dihydroartemisinin (DHA), using the Drosophila l(2)gl/l(2)gl loss-of-function mutant. DHA administration completely rescued the tumor phenotype in the brain and the wing discs in the Drosophila glioma model, improving survival. The behavioral assay conducted to correlate tumor suppression with the restoration of brain function demonstrated restored locomotory abilities comparable to those of the wild-type strain. DHA restored the wild-type cellular architecture in the optic lobes from a spatially disrupted state and transiently elevated reactive oxygen species to suprathreshold levels, suggesting an oxidative stress-mediated anti-oncogenic mechanism. Our work elucidated the therapeutic potential of DHA in vivo in Drosophila and opens up new avenues for further clinical validation with mammalian models and probing into the cellular networks involved in developing effective treatment strategies against glioma.