4'-O-Methylbroussochalcone B as a novel tubulin polymerization inhibitor suppressed the proliferation and migration of acute myeloid leukaemia cells.

ABSTRACT:

Background

Recent years, survival rates of human with high-risk acute myeloid leukaemia (AML) have not raised substantially. This research aimed to investigate the role of 4'-O-Methylbroussochalcone B, for the treatment of human AML.

Methods

Firstly, we evaluated the effects of six chalcones on AML cells activity by MTT assay. Immunofluorescence staining, tubulin polymerization assay and N,N'-ethylenebis (iodoacetamide) (EBI) competition assay were performed on ML-2 cells. Transwell and apoptosis assay were also utilized in ML-2 cells and OCI-AML5 cells. The expressions of migration-related proteins, apoptosis-related proteins and Wnt/?-catenin pathway were detected by Western Blot.

Results

The results found six chalcones exhibited the anti-proliferative activity against different AML cell lines. Based on the results of immunofluorescence staining, tubulin polymerization assay and EBI competition assay, 4'-O-Methylbroussochalcone B was discovered to be a novel colchicine site tubulin polymerization inhibitor. 4'-O-Methylbroussochalcone B could induce apoptosis, inhibit proliferation and migration of ML-2 cells and OCI-AML5 cells. The cells were arrested in the G2-M phase by the treatment of 4'-O-Methylbroussochalcone B. In addition, 4'-O-Methylbroussochalcone B regulated MAPK and Wnt/?-catenin pathways in AML cells.

Conclusion

4'-O-Methylbroussochalcone B might inhibit proliferation and migration of the AML cells by MAPK and Wnt/?-catenin pathways as a tubulin polymerization inhibitor. It is promising for 4'-O-Methylbroussochalcone B to become a new drug to treat AML.

SUBMITTER: Liu Z 

PROVIDER: S-EPMC7825173 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature