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

[Study on degradation kinetics or potassium dehydroandrographolidi succinas].

OBJECTIVE: To investigate the hydrolytic degradation of the kinetic characteristics of Potassium Dehydroandrographolidi Succinas (DAS-K) in aqueous solution. METHODS: The HPLC method was used to determine the degradation kinetic parameters of DAS-K aqueous solution at different initial concentration, different pH, different ionic strength. various temperatures and in different buffer solutions. RESULTS: DAS-K hydrolytic degradation followed first-order kinetics as measured by HPLC. From pH 8, the hydrolytic degradation rate of DAS-K markedly increased with pH. DAS-K was unstable in alkaline pH solution. The species of buffer solutions seem to have different impact on the catalytic process. The ionic strength did not have significant effect on the stability of the drug. According to the Arrhenius plot, the dependence of the decomposition on temperature was a determining factor, the activation energy was estimated to be 95.68 KJ/mol in phosphate buffer solution at pH 8 and temperature from 60 to 90 degrees C. CONCLUSION: It was found that the hydrolytic degradation of DAS-K complied with first-order kinetics. The rate of hydrolytic degradation of DAS-K depended on the pH of solution, the buffer concentration, the buffer species and the temperature. Especially, pH value was an important factor in determining the rate of the hydrolytic degradation of the drug.