Cargando…

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

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 AM...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Ziying, Wang, Changshui, Wang, Yali, Wang, Lei, Zhang, Yueyuan, Yan, Genquan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825173/
https://www.ncbi.nlm.nih.gov/pubmed/33482772
http://dx.doi.org/10.1186/s12885-020-07759-4
Descripción
Sumario: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/β-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/β-catenin pathways in AML cells. CONCLUSION: 4′-O-Methylbroussochalcone B might inhibit proliferation and migration of the AML cells by MAPK and Wnt/β-catenin pathways as a tubulin polymerization inhibitor. It is promising for 4′-O-Methylbroussochalcone B to become a new drug to treat AML. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-020-07759-4.