Lee Sang-Woo, Lee Jae-Tae, Lee Maan-Gee, Lee Ho Won, Ahn Sohn Joo, Lee Yong Jin, Lee You La, Yoo Jeongsoo, Ahn Byeong-Cheol, Ha Jeoung-Hee
Department of Nuclear Medicine, School of Medicine, Kyungpook National University, 101 Dongin 2-Ga, Jung-Gu, Daegu, Republic of Korea.
J Nat Med. 2009 Apr;63(2):124-9. doi: 10.1007/s11418-008-0300-x. Epub 2008 Dec 3.
The need for beneficial use of sedatives in oncologic patients is increasing. Therefore, in this study, antiproliferative characteristics of herbal and synthetic sedatives were examined in vitro in SNU-C4 human colorectal adenocarcinoma cells. Apigenin (50% inhibition concentration, IC(50) = 1.8 +/- 0.5 microM) and diazepam (IC(50) = 7.0 +/- 0.5 microM) showed concentration-dependent inhibition of SNU-C4 cancer cell survival. Efficacy of cancer cell survival inhibition by apigenin and diazepam was much lower than that of 5-fluorouracil (5-FU), a known chemotherapeutic drug. However, 10(-6) M concentration of apigenin and diazepam potentiated 5-FU-induced cytotoxicity. In SNU-C4 cells, 10(-6) M concentrations of diazepam, flumazenil (Ro15-1788), Ro5-4864, or PK11195, all ligands for central- or peripheral-type benzodiazepine (BZD) receptors, inhibited cell survival like the flavonoid apigenin (4',5,7-trihydroxyflavone) and fisetin (3,7,3',4'-tetrahydroxyflavone). Also like the plant flavonoids, treatment with 10(-6) M concentration of diazepam for 3 days hardly affect the peripheral-type BZD receptor (PBR) messenger RNA (mRNA) expression and inhibited glucose utilization of SNU-C4 cells. Treatment with flavonoids or diazepam for 6 days upregulated PBR mRNA expression and cell cytotoxicity of SNU-C4 cells. Furthermore, treatment with 10(-6) M concentration of apigenin, a natural sedative material originating from traditional herbs, positively modulated BZD-induced antiproliferative cytotoxicity in SNU-C4 cells. Overall, the in vitro antiproliferative activity on SNU-C4 cancer cells of herbal sedatives, such as apigenin, plus additive enhancement of synthetic BZD- and 5-FU-induced antiproliferative activities, were shown. In conclusion, this study provides experimental basis for advanced trial in the future.
肿瘤患者对使用有益镇静剂的需求日益增加。因此，在本研究中，在体外对SNU - C4人结肠直肠腺癌细胞检测了草药和合成镇静剂的抗增殖特性。芹菜素（50%抑制浓度，IC50 = 1.8±0.5微摩尔）和地西泮（IC50 = 7.0±0.5微摩尔）对SNU - C4癌细胞存活表现出浓度依赖性抑制。芹菜素和地西泮对癌细胞存活抑制的效力远低于已知化疗药物5 - 氟尿嘧啶（5 - FU）。然而，10^(-6) M浓度的芹菜素和地西泮增强了5 - FU诱导的细胞毒性。在SNU - C4细胞中，10^(-6) M浓度的地西泮、氟马西尼（Ro15 - 1788）、Ro5 - 4864或PK11195，所有这些中枢或外周型苯二氮䓬（BZD）受体的配体，都像类黄酮芹菜素（4',5,7 - 三羟基黄酮）和非瑟酮（3,7,3',4' - 四羟基黄酮）一样抑制细胞存活。同样像植物类黄酮一样，用10^(-6) M浓度的地西泮处理3天几乎不影响外周型BZD受体（PBR）信使核糖核酸（mRNA）表达，并抑制SNU - C4细胞的葡萄糖利用。用类黄酮或地西泮处理6天上调了SNU - C4细胞的PBR mRNA表达和细胞毒性。此外，用10^(-6) M浓度的芹菜素（一种源自传统草药的天然镇静物质）处理，在SNU - C4细胞中正向调节了BZD诱导的抗增殖细胞毒性。总体而言，显示了草药镇静剂如芹菜素对SNU - C4癌细胞的体外抗增殖活性，以及合成BZD和5 - FU诱导的抗增殖活性的加性增强。总之，本研究为未来的进一步试验提供了实验依据。
