Anti-breast cancer activity of ebracteolatain A / 第二军医大学学报

ABSTRACT

Objective To isolate and purify ebracteolatain A from the roots of Euphorbia ebracteolata Hayata, and to explore its anti-breast cancer activity. Methods Ebracteolatain A was isolated and purified from the roots of Euphorbia ebracteolata Hayata using reflux extraction, solvent extraction and absorption chromatography techniques. The chemical structure was identified by mass spectrometry and nuclear magnetic resonance spectrometry. The antibreast cancer activity of ebracteolatain A was determined by MTT assay in the breast cancer cell lines including SUM149 (triple-negative), MCF-7 (luminal A), ZR-75-1 (luminal B) and SK-BR-3 (HER2-positive). The effect of ebracteolatain A on cell cycle was determined by flow cytometry. A tumor model was established in nude mice by transplanting SUM149 cells, and the inhibitory effect of ebracteolatain A on breast cancer was evaluated. Results The ebracteolatain A was 3, 3’-diacetyl-2, 4’-dimethoxy-2’, 4, 6, 6’-tetrahydroxy-5’-methyl diphenylmethane. The half maximal inhibitory concentrations of ebracteolatain A on SUM149, MCF-7, ZR-75-1 and SK-BR-3 cells were 5.50, 6.16, 7.08 and 8.64 μmol/L, respectively. With the increase of drug concentration (2.5, 5, 10 μmol/L), the percentage of the cells at G0/G1 phase was decreased (P<0.05, P<0.01) and the percentage of the cells at S phase was increased (P<0.05, P<0.01) after treatment with ebracteolatain A for 12, 24 and 48 h. After intraperitoneal injection of ebracteolatain A 35 mg/kg, the inhibition rates of the tumor volume and mass in nude mice were 37.94% and 41.38%, respectively. Conclusion Ebracteolatain A can inhibit the proliferation of the four types of breast cancer cells and the growth of transplanted-SUM149 cell tumor on nude mice, which may be related to suppressing the transition of cell cycle from S phase to G2/M phase.