Background
In childhood, metastatic neuroblastoma (NB) is the most common extracranial solid tumor, but there are no appropriate drugs for its treatment. Dihydroartemisinin (DHA), a drug for malaria treatment, has therapeutic potential in several cancers; however, its mechanisms remain unclear. This study aimed to investigate the anti-proliferation effect of DHA on SH-SY5Y cells and to explore its mechanism in vitro.
Conclusions
These data suggest that DHA could regulate taurine, linoleic acid, phenylalanine metabolism, and tryptophan metabolism, which are involved in the anti-proliferation effect of DHA in SH-SY5Y cells.
Methods
We used 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to measure the half-maximal inhibitory concentration (IC50) of DHA; western blot was used to determine protein levels; propidium iodide (PI) staining was used to determine apoptotic cells; JC-1 staining to measure mitochondrial membrane potential; and dichloro-dihydro-fluorescein diacetate (DCFH-DA) staining was used to determine reactive oxygen species (ROS). Metabonomic analysis was performed by using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS)-based untargeted metabolomics. Multivariate statistical analysis was performed to screen potential metabolites associated with DHA treatment in SH-SY5Y cells.
Results
It was shown that DHA inhibited SH-SY5Y cell proliferation and increased poly (ADP-ribose) polymerase (PARP-1) and caspase 3 in a dose-dependent manner. In Further, DHA promoted ROS generation and γH2AX expression. In addition, a total of 125 proposed metabolites in SH-SY5Y cells and 45 vital metabolic pathways were identified through UHPLC-MS/MS-based untargeted metabolomic analysis. Conclusions: These data suggest that DHA could regulate taurine, linoleic acid, phenylalanine metabolism, and tryptophan metabolism, which are involved in the anti-proliferation effect of DHA in SH-SY5Y cells.