Growth inhibitory and apoptosis inducing by effects of total flavonoids from Lysimachia clethroides Duby in human chronic myeloid leukemia K562 cells

Ethnopharmacological relevance: Lysimachia clethroides Duby is a traditional Chinese medicinal herb has been used in China to treat edema, jaundice diseases, hepatitis, tumor and inflammations, but the anti-tumor mechanisms are unclear. Aim of the study: The present study was undertaken to investigate if total flavonoids from Lysimachia clethroides Duby (ZE4) possesses anti-cancer effects through apoptotic pathways in human chronic myeloid leukemia K562 cells. Materials and methods: K562 cells were treated with different concentrations of ZE4 at different time intervals. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis was assessed by flow cytometry, Hoechst 33258 staining and COMET assay. Western blot analysis was used to detect Bcl-2, Trail and DR5 expressions. Results: 15 flavonoids were isolated and identified from ZE4. ZE4 could inhibit the growth of K562 cells significantly by induction of apoptosis. Marked morphological changes of apoptosis, DNA fragmentation and single DNA strand breakages were observed clearly after treatment of ZE4. Bcl-2 expression was down-regulated remarkably while Fas, Trail and DR5 up-regulated when apoptosis occurred. Conclusions: This result suggests that total flavonoids of Lysimachia clethroides Duby exert potential anti-cancer activity through growth inhibition and apoptosis in K562 cells. [Copyright &y& Elsevier]