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

  • BMC Cancer. 2021 Jan 22;21(1):91. doi: 10.1186/s12885-020-07759-4.
Ziying Liu  1 ,  Changshui Wang  2 ,  Yali Wang  2 ,  Lei Wang  2 ,  Yueyuan Zhang  2 ,  Genquan Yan  3
Affiliations
  • 1. Department of pediatrics, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, China.
  • 2. Department of Clinical & Translational Medicine, Jining Life Science Center, Jining, China.
  • 3. Department of pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China. [email protected].
PMID: 33482772 DOI: 10.1186/s12885-020-07759-4
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/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.

Keywords
4′-O-Methylbroussochalcone B; Acute myeloid leukaemia; Colchicine; Migration; Tubulin polymerization inhibitor.
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