Inhibitory activities of Lignum Sappan extractives on growth and growth-related signaling of tumor cells

AIM:To investigate the active constituents of Lignum Sappan(Caesalpinia sappan L.) on growth-related signaling and cell mitosis.METHOD:The influence of the ethyl acetate(EtOAc) extract of Lignum Sappan and its constituents on growth-related signaling were evaluated by a luciferase assay in cells stably-transfected with NF-B,STAT1,or STAT3 responsive luciferase reporter plasmid.The inhibitory effect on the cell cycle was determined by flow cytometric analysis.The anti-tumor activities were assessed in vitro and in vivo.RESULTS:The EtOAc extract of Lignum Sappan had inhibitory activities on growth-related signaling and cell mitosis.Three major active compounds were sappanchalcone,brazilin,and butein.Sappanchalcone blocked cell cycle progression in the G2/M phase,brazilin inhibited TNF/NF-B signaling,while butein inhibited IL-6/STAT3 signaling,as well as TNF/NF-B signaling.The three compounds all demonstrated cytotoxic activities against human tumor cells in vitro.In a S180 tumor cell-bearing mice model,the anti-tumor efficacy of the EtOAc extract was better than the individual compounds acting alone.CONCLUSION:These results indicate that Lignum Sappan contains multiple active compounds with different antitumor activities,which act synergistically to enhance their anti-tumor effects.The EtOAc extract of Lignum Sappan may be better than individual active constituent as a novel medicine for the treatment of cancer.