Chikusetsusaponin IVa Methyl Ester Induces G1 Cell Cycle Arrest, Triggers Apoptosis and Inhibits Mig

来源 :中华中医药学会中药实验药理分会第十二次学术会议 | 被引量 : 0次 | 上传用户:litao343243581
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  Purpose: Panacis Japonici Rhizoma(PJR)is one of the most famous Chinese medical herbs and presents potential anti-cancer effects.This study aims to isolate and investigate the anti-cancer potential of saponins from PJR on ovarian cancer cells.Methods: The compounds were separated by a silica gel column.By comparison of the 1H-NMR and 13C-NMR data,as well as HR-ESI-MS data,with the corresponding references,compounds were determined.MTT assay was performed to evaluate cell viability,along with flow cytometry for cell cycle analysis.JC-1 staining,Annexin V-PI double staining as well as Hoechst 33342 staining were used for detecting cell apoptosis.Western blotting was conducted to determine the relative protein level.Transwell assay was performed to investigate the effect of the saponins on cell migration and invasion.Results: Eleven saponins were isolated from PJR and their anti-proliferative effects were evaluated on human ovarian cancer cells.Chikusetsusaponin IVa methyl ester(1)exhibited the highest anti-proliferative potential among these isolates with the IC50 values less than 10 μM in both ovarian cancer A2780 and HEY cell lines.Compound 1 induced G1 cell cycle arrest accompanied with an S phase decrease.Further study showed that compound 1 effectively decreased cell mitochondrial membrane potential,increased annexin V positive cells and nuclear chromatin condensation,as well as enhanced the expression of cleaved-PARP.Moreover,compound 1 obviously suppressed the migration and invasion of HEY and A2780 cells.Conclusion: These results provide a rationale evaluation of compound 1 as a potential compound for the treatment of ovarian cancer.
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