3 research outputs found
Triptolide-mediated cell death in neuroblastoma is cell line dependent and occurs by multiple mechanisms
Triptolide and sorafenib combination therapy in hepatocellular carcinoma results in superior cell death in vitro and prolonged survival in vivo
Triptolide-mediated cell death in neuroblastoma occurs by both apoptosis and autophagy pathways and results in inhibition of nuclear factor–kappa B activity
Neuroblastoma is an aggressive pediatric malignancy with significant chemotherapeutic resistance. We assessed triptolide as a potential therapy.
SH-SY5Y and IMR-32 neuroblastoma cell lines were treated with triptolide. Viability, intracellular calcium, caspase activation, protein, and mRNA levels were measured. Autophagy was evaluated with confocal microscopy. Nuclear factor–kappa B (NF-κB) activation was measured using a dual luciferase assay.
Triptolide treatment resulted in death in both cell lines within 72 hours, with sustained increases in intracellular calcium. IMR-32 cells underwent cell death by apoptosis. Conversely, light chain 3II (LC3II) protein levels were elevated in SH-SY5Y cells, which is consistent with autophagy. Confocal microscopy confirmed increased LC3 puncta in SH-SY5Y cells compared with control cells. Heat shock pathway protein and mRNA levels decreased with treatment. NF-κB assays demonstrated inhibition of tumor necrosis factor (TNF)-α–induced activity with triptolide.
Triptolide treatment induces cell death in neuroblastoma by different mechanisms with multiple pathways targeted. Triptolide may serve a potential chemotherapeutic role in advanced cases of neuroblastoma