SEARCH FOR ANTI-METASTATIC AND DIFFERENTIATION-INDUCING ACTIVE COMPOUNDS FROM MEDICINAL PLANTS AND FOODS

在本研究中，我们研究了药用植物中具有抗侵袭性、抑制基质金属蛋白酶（MMPs）产生、诱导分化活性的活性成分，这些活性成分已被用于抗癌和长寿。通过体外matrigel包被筛选，发现泰国传统药材丹参（Convolvulaceae）茎的MeOH提取物和etoac可溶部位可抑制HT1080细胞的侵袭，并抑制人成纤维细胞（HT1080）和人白血病细胞（U937）细胞的增殖。通过生物测定引导分离，从乙酸乙酯馏分中分离出四种主要的鱼素[去鱼胶素(1)、鱼松素(2)、鱼藤酮(3)、12a-羟基鱼藤酮(4)]以及各种异黄酮和翼龙烷类化合物。其中1 ~ 4种在3 ~ 30 μM孵育24 h后抑制HT1080细胞的侵袭，48 h后抑制HT1080和人白血病U937细胞的增殖。明胶酶谱分析表明，1-4 （1-10 μM）对培养基中promp -9的释放有较强的抑制作用。此外，化合物1和2 （10 μM）通过NBT还原实验诱导HL-60细胞分化。在抗侵袭实验中，发现白花楸根茎甲醇提取物及其生物碱组分对小鼠黑色素瘤细胞（B16F10）和HT1080均有细胞毒作用。具有6-羟基的二聚倍半萜硫代生物碱（6-羟基噻吩乌帕啶，6,6'-二羟基噻吩乌帕啶，6 -羟基噻吩乌帕啶B）在10 μM浓度下显示出明显的细胞毒活性，并澄清了活性的几个结构要求。6-羟基硫代比乌啶处理后1 h内立即观察到U937细胞凋亡，发现其凋亡途径与caspase-8有关。此外，从用于癌症治疗的黑草种子中分离到了新的二萜生物碱——黑草胺，并确定了它们的化学结构。1'S-1'-乙酰基chavicol乙酸酯及多种相关化合物可抑制NF-κB的活化，提示其具有抗肿瘤活性。少

In the present study, we investigated the active constituents with anti-invasive, matrix metalloproteases (MMPs) production inhibitory, differentiation-inducing activities from medicinal plants that have been used for anti-cancer and longevity.1.The MeOH extract and EtOAc-soluble fraction traditional Thai medicine, the stems of Erycibe expansa (Convolvulaceae) were found to inhibit invasion of HT1080 cells through Matrigel-coated filters in vitro and proliferation of human fibroblast (HT1080) and human leukemia cell (U937) cells. Through bioassay-guided separation, four principal rotenoids [deguelin (1), tephrosin (2), rotenone (3), 12a-hydroxyrotenone (4)] together with various isoflavones and pterocarpanes were isolated from the EtOAc fraction. Among them, 1-4 inhibited the invasion of HT1080 cells at 3-30 μM after 24 h incubation, and they also inhibited proliferation of HT1080 and human leukemia U937 cells after 48 h incubation. With regard to their action mechanism, 1-4 (1-10 μM) … More inhibited release of proMMP-9 in the medium using a gelatin zymography. Furthermore, compounds 1 and 2 (10 μM) induced the differentiation of HL-60 cells using NBT reduction test.2.The methanolic extract and its alkaloid fraction from the rhizomes of Nuphar pumilum were found show cytotoxic effects on U937, mouse melanoma cell (B16F10), and HT1080 in the experiments of their anti-invasion. Dimeric sesquiterpene thioalkaloids with the 6-hydroxyl group (6-hydroxythiobinupharidine, 6,6'-dihydroxythiobinupharidine, 6-hydroxythionuphlutine B) showed substantial cytotoxic activity at a concentration of 10 μM, and several structural requiremwnts for the activity were clarified. Apoptosis of U937 was immediately observed within 1 h after treatment of 6-hydroxythiobinupharidine and pathway via caspase-8 was found to be involved.3.Furthermore, new diterpene alkaloids, nigellamines were isolated from the seeds of Nigella sativa that have been used for cancer treatment and their chemical structures were determined. 1'S-1'-Acetoxychavicol acetate and various related compounds were found to inhibit activation of NF-κB, suggesting antitumor activity. Less