Echium arenarium Guss is a Mediterranean plant traditionally used in healing skin wound and it was reported exhibiting potent antioxidant, antibacterial, and antiparasitic activities. However, antitumoral activities of this plant have not yet been explored. Here we investigated for the first time, root (EARE) and aerial part (EAAPE) extracts of E. arenarium Guss to examine cytotoxicity and apoptosis activation pathway on U266 human multiple myeloma (MM) cell line. We demonstrated that EARE and EAAPE decreased U266 cell viability in a dose dependent manner. Based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, EARE was significantly two times more efficient (IC50 value 41 μg/ml) than EAAPE (IC50 value 82 μg/ml) considering 48 h of treatment. Furthermore, after 24 h of exposure to 100 μg/ml of EARE or EAAPE, cell cycle showed remarkable increase in sub-G1 population and a decrease of U266 cells proportion in G1 phase. In addition, EARE increased cell percentage in S phase. Moreover, analysis revealed that EAAPE or EARE induced apoptosis of U266 cells after 24 h of treatment. Interestingly, depolarization of mitochondrial membrane potential and activation of caspase 3/7 were demonstrated in treated U266 cells. Phytochemical analysis of E. arenarium extracts showed that EARE exhibited the highest content of total phenolic content. Interestingly, six phenolic compounds were identified. Myricitrin was the major compound in EARE, followed by luteolin 7-O-glucoside, resorcinol, polydatin, Trans-hydroxycinnamic acid, and hyperoside. These findings proved that an intrinsic mitochondria-mediated apoptosis pathway probably mediated the apoptotic effects of E. arenarium Guss extracts on U266 cells, and this will suggest several action plans to treat MM.

中文翻译：

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Echium arenarium Guss 水甲醇根和地上部分提取物通过线粒体途径抑制多发性骨髓瘤细胞增殖并诱导其凋亡

Echium arenarium Guss 是一种地中海植物，传统上用于治疗皮肤伤口，据报道它具有强大的抗氧化、抗菌和抗寄生虫活性。然而，尚未探索该植物的抗肿瘤活性。在这里，我们首次研究了 E. arenarium Guss 的根 (EARE) 和地上部分 (EAAPE) 提取物，以检查 U266 人多发性骨髓瘤 (MM) 细胞系的细胞毒性和细胞凋亡激活途径。我们证明 EARE 和 EAAPE 以剂量依赖性方式降低 U266 细胞活力。基于 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物测定，考虑到 EARE 的效率（IC50 值 41 μg/ml）是 EAAPE（IC50 值 82 μg/ml）的两倍治疗48小时。此外，暴露于 100 μg/ml EARE 或 EAAPE 24 小时后，细胞周期显示亚G1期细胞数量显着增加，G1期U266细胞比例下降。此外，EARE 增加了 S 期的细胞百分比。此外，分析显示EAAPE或EARE在处理24小时后诱导U266细胞凋亡。有趣的是，在处理过的 U266 细胞中证实了线粒体膜电位的去极化和 caspase 3/7 的激活。E. arenarium 提取物的植物化学分析表明，EARE 的总酚含量最高。有趣的是，鉴定了六种酚类化合物。杨梅素是 EARE 中的主要化合物，其次是木犀草素 7-O-葡萄糖苷、间苯二酚、虎杖苷、反式羟基肉桂酸和金丝桃苷。这些发现证明内在的线粒体介导的细胞凋亡途径可能介导了大肠杆菌的凋亡作用。