Introduction
Medulloblastoma is a major cause of paediatric braintumours worldwide. Whilst effective, current treatmentsare often associated with lifelong off-target effectsresulting in lower quality of life and early mortality inpaediatric patients. This necessitates the need to developnew therapies. One source of novel chemotherapeuticsare those derived from plants, as they are associated with potent effects along with lesser off-target effects (Jones etal., 2023). One species, Tripterygium wilfordii, has gained interest over the last decade for the treatment of cancers. Whilst many compounds from this species have shown anti-cancer efficacy, triptonide, has garnered interest due to its diverse biological activity, including the induction of apoptosis and cell cycle arrest in multiple cancer cell types (Song et al., 2023). However, the efficacy of triptonide against medulloblastoma subtypes is limited. To address this, we sought to elucidate the anti-medulloblastoma efficacy of triptonide.
Material and method
The effect of triptonide on medulloblastoma (HD-MB-03, & DAOY) viability was determined using MTT and washout assays. Time-lapse live-cell microscopy was utilised to examine the effect of triptonide on cellmorphology and cell fate profile. Flow cytometry was used to examine the cell death mechanism (Annexin V/Propidium Iodide), and mitochondrial membrane potential (Rhodamine 123) [1].
Result and discussion
Triptonide produced time and concentration-dependentirreversible decreases in viability against both HD-MB-03 and DAOY cell lines, with IC50 values of 11 nM and0.64 µM respectively after exposure for 72 hrs. HD-MB-03 cell fate profiling found triptonide (5 nM)significantly increased total cell cycle time by 118.4 ±22.6 % (P < 0.0001) compared to control. All concentrations examined (5-20nM) resulted in asignificant concentration-dependent increase in cellulardeath in interphase (P < 0.0001) and produced morphological changes associated with apoptosis. Flow cytometry revealed treatment with triptolide (20 nM) significantly increased apoptosis 5.2-fold (P = 0.046) compared to control. Triptonide also significantlydecreased mitochondrial membrane potential (42.8 ±6.7 %, P = 0.006), indicative of intrinsic apoptosis.
Conclusion
These findings suggest that triptonide shows promise as atreatment for group 3 medulloblastoma subtypes throughthe induction of apoptosis. Further research is nowrequired to determine the molecular mechanisms ofaction underpinning this observed activity.
[1] The study was ethically approved by the University of Salford EthicalReview Board (ID: 10513)
Presentation Conference Type
Conference Abstract
Conference Name
European Association for Cancer Research Annual Congress 2025
