在我们之前的工作中,间壁(1mg/mL)的青霉(AC)地上部分和Ixoracoccinea(IC)叶显示出94%和96%的抑制作用,分别,而它们的馏分显示IC5043和116微克/毫升,分别,针对基质金属蛋白酶9(MMP9),一种催化细胞外基质蛋白水解的酶。在本研究中,我们对AC正己烷进行了IC50测定,IC正己烷,和IC乙酸乙酯分区,其次是单个分区对MDA-MB-231,4T1,T47D的细胞毒性研究,MCF7和Vero细胞系。从AC正己烷和IC乙酸乙酯分区的连续分馏导致两种化合物的分离,土霉素(OTC)和邻苯二甲酸二辛酯(DOP)。结果表明,AC正己烷,IC正己烷,和IC乙酸乙酯分区抑制MMP9,其各自的IC50如下:246.1µg/mL,5.66微克/毫升,和2.75×10-2µg/mL。向MDA-MB-231,4T1,T47D,MCF7、AC正己烷显示IC502.05、265、109.70和2.11µg/mL,分别,而IC乙酸乙酯显示IC50为1.92、57.5、371.5和2.01µg/mL,分别。OTC对MMP9的抑制作用由其IC5018.69µM表示,而DOP不活跃。分子对接研究表明,OTC更喜欢结合PEX9而不是其催化结构域。对于4T1,OTC显示出IC50为414.20μM的抑制作用。总之,这项研究进一步支持了先前的发现,即AC和IC是两种有可能被开发为三阴性抗乳腺癌药物的草药。
In our previous work, the partitions (1 mg/mL) of Ageratum conyzoides (AC) aerial parts and Ixora coccinea (IC) leaves showed inhibitions of 94% and 96%, respectively, whereas their fractions showed IC50 43 and 116 µg/mL, respectively, toward Matrix Metalloproteinase9 (MMP9), an enzyme that catalyzes a proteolysis of extracellular matrix. In this present
study, we performed IC50 determinations for AC n-hexane, IC n-hexane, and IC ethylacetate partitions, followed by the cytotoxicity
study of individual partitions against MDA-MB-231, 4T1, T47D, MCF7, and Vero cell lines. Successive fractionations from AC n-hexane and IC ethylacetate partitions led to the isolation of two compounds, oxytetracycline (OTC) and dioctyl phthalate (DOP). The result showed that AC n-hexane, IC n-hexane, and IC ethylacetate partitions inhibit MMP9 with their respective IC50 as follows: 246.1 µg/mL, 5.66 µg/mL, and 2.75 × 10-2 µg/mL. Toward MDA-MB-231, 4T1, T47D, and MCF7, AC n-hexane demonstrated IC50 2.05, 265, 109.70, and 2.11 µg/mL, respectively, whereas IC ethylacetate showed IC50 1.92, 57.5, 371.5, and 2.01 µg/mL, respectively. The inhibitions toward MMP9 by OTC were indicated by its IC50 18.69 µM, whereas DOP was inactive. A molecular docking
study suggested that OTC prefers to bind to PEX9 rather than its catalytic domain. Against 4T1, OTC showed inhibition with IC50 414.20 µM. In conclusion, this
study furtherly supports the previous finding that AC and IC are two herbals with potential to be developed as triple-negative anti-breast cancer agents.