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.

• Authors: Yanna Ma, Ying Li, Mei Huang, Yuesheng Meng
• Journal: Journal of chemotherapy (Florence, Italy) (J Chemother) Vol. 35 Issue 3 Pg. 240-249 (May 2023) ISSN: 1973-9478 [Electronic] England
• PMID: 35666085 (Publication Type: Journal Article)

Chemical References

• triptolide

Topics

• Adult
• Humans
• Wnt Signaling Pathway
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, genetics)
• Cell Line, Tumor
• Epigenesis, Genetic
• T-Lymphocytes