Medulloblastoma is a common cause of childhood cancer, accounting for 20-25% of paediatric brain tumours worldwide. Whilst current treatments are effective, they are associated with off-target effects, impacting patients’ quality of life for decades after remission. This necessitates the development of new therapies, with phytochemicals offering potential novel sources. Recent evidence suggests compounds from Tripterygium wilfordii exert anti-cancer effects. However, there is limited evidence of this in medulloblastoma. To address this, we sought to elucidate the fundamental anti-medulloblastoma effect of Tripterygium wilfordii-derived compounds.
The effect of two Tripterygium wilfordii-derived compounds (celastrol and triptolide) on medulloblastoma (HD-MB-03 & DAOY) viability was determined using MTT and washout assays. Time-lapse live-cell microscopy was used to examine cell morphology, cell fate profile and cellular migration. Flow cytometry examined the cell death mechanism (Annexin V/Propidium Iodide). This study was ethically approved by the University of Salford Ethical Review Board (ID:10513).
Both celastrol and triptolide induced irreversible concentration and time-dependent decreases in both HD-MB-03 and DAOY viability with IC50 values of 151-232nM and 18-169nM respectively. Cell fate profiling highlighted significant increases in morphological hallmarks of apoptosis (cell shrinkage & blebbing). Flow cytometry revealed significant increases in apoptotic cells following exposure to both compounds (P<0.001). No effect on cell migration was observed following exposure to triptolide. Celastrol significantly decreased bulk cell migration by 50.4±3.8% (P=0.0002). Single-cell migration analysis revealed significant decreases in cell migratory distance and speed (30.4±4.1%, P<0.0001).
These data highlight the potential of celastrol and triptolide as treatments for medulloblastoma. Further work is now required to elucidate the molecular mechanisms of action.
