Department of pediatrics, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, China.
Department of Clinical & Translational Medicine, Jining Life Science Center, Jining, China.
BMC Cancer. 2021 Jan 22;21(1):91. doi: 10.1186/s12885-020-07759-4.
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.
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.
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.
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.
近年来，高危急性髓系白血病（AML）患者的生存率并未显著提高。本研究旨在探讨 4'-O-甲基川陈皮素 B 治疗人类 AML 的作用。
首先，我们通过 MTT 测定法评估了六种查耳酮对 AML 细胞活性的影响。对 ML-2 细胞进行免疫荧光染色、微管聚合试验和 N，N'-亚乙基双（碘乙酰胺）（EBI）竞争试验。还在 ML-2 细胞和 OCI-AML5 细胞中进行了 Transwell 和凋亡试验。通过 Western Blot 检测迁移相关蛋白、凋亡相关蛋白和 Wnt/β-catenin 通路的表达。
结果发现六种查耳酮对不同的 AML 细胞系均表现出抗增殖活性。基于免疫荧光染色、微管聚合试验和 EBI 竞争试验的结果，发现 4'-O-甲基川陈皮素 B 是一种新型秋水仙碱结合部位微管聚合抑制剂。4'-O-甲基川陈皮素 B 可诱导 ML-2 细胞和 OCI-AML5 细胞凋亡、抑制增殖和迁移。用 4'-O-甲基川陈皮素 B 处理可使细胞停滞在 G2-M 期。此外，4'-O-甲基川陈皮素 B 调节 AML 细胞中的 MAPK 和 Wnt/β-catenin 通路。
4'-O-甲基川陈皮素 B 可能通过 MAPK 和 Wnt/β-catenin 通路作为微管聚合抑制剂抑制 AML 细胞的增殖和迁移。作为一种新的治疗 AML 的药物，4'-O-甲基川陈皮素 B 具有广阔的前景。
