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Triptolide induces pro-apoptotic effects against medulloblastoma subtypes

Eastham, Hannah; Morovis Marchetti Cassarotti, Julia; Yaqoob, Marriam; Samphire-Noden, Bethan; Greensmith, David; Jones, Matthew

Authors

Hannah Eastham

Julia Morovis Marchetti Cassarotti

Marriam Yaqoob

Bethan Samphire-Noden



Abstract

Introduction
Medulloblastoma is a common cause of cancer in children, accounting for 20-25% of all paediatric brain tumours worldwide (de Medeiros et al., 2019). Whilst current treatments are effective, they are associated with substantial off-target effects, which impact patients’quality of life for decades after remission is achieved (Jones et al., 2023). This necessitates the need for the development of new treatments, with phytochemicals offering a novel source of new compounds. Extracts of Tripterygium wilfordii have been used in Traditional Chinese Medicine for centuries (Shan et al., 2023), with recent evidence suggesting that compounds derived from this species, such as Triptolide, exert anti-cancer effects (Noel et al., 2019). However, there is no evidence of if this effect translates to medulloblastoma. To address this, we sought to elucidate the fundamental anti-medulloblastoma effect of triptolide.

Material and method
The effect of triptolide on medulloblastoma (HD-MB-03,& DAOY) viability was determined using MTT, long-term proliferation and washout assays. Time-lapse live-cell microscopy was utilised to examine the effect of triptolide on cell morphology, cell fate profile and cellular migration. Flow cytometry was used to examine the cell death mechanism (Annexin V/Propidium Iodide) [1].

Result and discussion
Triptolide produced irreversible concentration and time-dependent decreases in medulloblastoma viability in both HD-MB-03 and DAOY cells, with IC50 values afterexposure for 72 hours found to be 18 nM and 169 nM respectively. HD-MB-03 cell fate profiling revealed that exposure to triptolide (10 nM) produced significantconcentration-dependent increases in cellular death within interphase (P < 0.0001) and a significant 38.5 ± 6.9 % increase in the time take to progress through thecell cycle compared to control (P < 0.0001). Morphological analysis showed triptolide to induce blebbing andcellular shrinkage, indicative of apoptosis. Flow cytometric analysis confirmed this, with a significant 5.2-fold increase in apoptotic cells (P = 0.0002) following treatment with triptolide (20 nM) for 72 hours. Triptolide produced no significant impact on cellular migration at all concentrations (5-20 nM) examined.

Conclusion
These data highlight the potential of triptolide as a novel potent treatment for medulloblastoma. Further work is now required to elucidate the molecular mechanism ofaction associated with the observed pro-apoptotic effect.
[1] The study was ethically approved by the University of Salford Ethical Review Board (ID: 3582).

Presentation Conference Type Conference Abstract
Conference Name European Association for Cancer Research Congress 2025
Start Date Jun 16, 2025
End Date Jun 19, 2025
Acceptance Date Apr 8, 2025
Online Publication Date Jun 11, 2025
Publication Date Jun 11, 2025
Deposit Date Jun 12, 2025
Print ISSN 1574-7891
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 19
Issue S1
Pages 523-524
DOI https://doi.org/10.1002/1878-0261.70070