甘草查尔酮类化合物对人肝癌Bel-7402细胞的抗癌活性研究

Anticancer activity of Licorice chalcone derivatives in Human Bel-7402 hepatocarcinoma cell lines

目的以天然查尔酮类化合物异甘草素(ILG)为先导物进行结构修饰,制备3-甲氧基异甘草素(3-MO-ILG),并研究ILG与3-MO-ILG的体外抗癌活性。方法利用酸催化的羟醛缩合反应制备ILG与3-MO-ILG目标化合物;应用人肝癌Bel-7402细胞为体外模型,用MTT法观察2种化合物对肝癌细胞增殖的抑制活性;用流式细胞仪测定促Bel-7402细胞凋亡能力;用张氏肝细胞(chang liver)测定对正常细胞的毒性。结果化合物ILG和3-MO-ILG对正常肝细胞无明显毒性,而对肝癌Bel-7402细胞的增殖有一定的抑制活性,浓度在5～200μg/mL范围内,对肝癌Bel-7402细胞的抑制率分别为23.28%～80.01%及41.96%～86.10%;2种化合物对肝癌细胞有明显的促进凋亡作用,最高凋亡率分别可达85%和93.5%。结论人肝癌Bel-7402细胞对甘草查尔酮类化合物具有较高的敏感性;ILG衍生物对人肝癌Bel-7402细胞增殖的抑制活性呈浓度依赖性,而对正常细胞的毒性明显小于对癌细胞的毒性;其抗癌作用机制可能是通过增殖抑制和促进凋亡来产生。本研究为甘草查尔酮类化合物中筛选抗肝癌候选药物奠定一定基础。

Objective To synthesize hydroxy-chalcone derivative 3-methyl-oxy-isoliquiritigenin （3-MO-ILG） within Isoliquiritigenin （ILG） as lead compound; and to study their anticancer activity in vitro. Methods The acid catalized reaction of aldolization was used for preparing the target compounds; human Bel-7402 hepatocarcinoma cells were treated with ILG and 3-MO-ILG, and cell viability and cellular apoptosis were determined by MTT method and flow cytometry, respectively; normal chang liver cells were used for testing their cytotoxicity. Results The two compounds （ILG and 3-MO-ILG） showed less cytotoxicity to change liver normal cells, however significant inhibitory activity towards Bel-7402 cancer cell proliferation, at the concentration range of 5-200 μg/mL, their inhibition activity reached 23. 28% -80. 01% and 41.96%-86.01%, respectively; the cellular apoptotic intensity was up to 85% and 93.5%. Conclusion Human Bel-7402 hepatocarcinoma cells have a relatively high sensitivity to the anticancer mechanism of the licorice chaleone derivatives, wich present a dose-dependent inhibition to hepatoma Bel-7402 cell proliferation and less cytotoxicity to normal hepatoma cells. Our works may provide an initial base for pharmaco-logical screening of new bioactive compounds from licochalcone derivatives with antihepatocancer potency.