Triptolide inhibits T-cell acute lymphoblastic leukaemia by affecting aberrant epigenetic events in the Wnt signalling pathway

Abstract

T-cell acute lymphoblastic leukaemia (T-ALL) is an aggressive haematologic disease that accounts for 15% of childhood and 25% of adult ALL cases. Triptolide (TPL) is an active component of Tripterygium wilfordii and was recently discovered to suppress the growth of some cancers, including ALL, but the underlying mechanism has yet to be elucidated. Dysfunction of the Wnt signalling pathway has been reported to be an important event in the pathogenesis of T-ALL. In this study, we investigated the effects of TPL on the Wnt pathway and found that it suppressed the expression of TCF7, C-MYC and β-catenin in T-ALL cell lines. Then, we indicated that TPL induced the expression of Wnt pathway antagonists, including WIF1, SOX17, CDH1 and SFRP5, in T-ALL cells. Further analysis indicated that TPL induced the demethylation of these genes, which may be related to the inhibited expression of methyltransferases DNMT1 and DNMT3a. In conclusion, our results suggest that TPL inhibits T-ALL by inhibiting aberrant epigenetic events in dysregulated Wnt signalling.

Keywords:

• Wnt signalling pathway
• T-cell acute lymphoblastic leukaemia
• Wnt antagonists
• triptolide
• epigenetics

Acknowledgement

We would like to thank all the authors for their contributions.

Disclosure statement

There are no conflicts of interest.

Authors’ contribution

Yanna Ma was responsible for the experimental operations, data analysis and article writing. Ying Li analysed the data. Yuesheng Meng and Mei Huang conceived and designed the study and obtained funding.

Additional information

Funding

This work was supported by the Youth Fund project of Shanghai Jinshan District Health Commission, China (No. JSKJ-KTQN-2019-02).