Department of Biology, American University of Beirut, Riad El-Solh, Beirut, Lebanon.
J Nat Med. 2013 Jul;67(3):468-79. doi: 10.1007/s11418-012-0703-6. Epub 2012 Sep 14.
We have previously shown that the two sesquiterpene lactones, salograviolide A (Sal A) and iso-seco-tanapartholide (TNP), isolated from the Middle Eastern indigenous plants Centaurea ainetensis and Achillea falcata, respectively, possess selective antitumor properties. Here, we aimed to assess the anticancer effects of the separate compounds and their combination, study their potential to generate reactive oxygen species (ROS), and investigate their underlying antitumor mechanisms in human colon cancer cell lines. Cells were treated with Sal A and TNP alone or in combination, and cell viability, cell cycle profile, apoptosis, ROS generation and changes in protein expression were monitored. Sal A and TNP in combination caused 80% decrease in HCT-116 and DLD-1 cell viability versus only 25% reduction when the drugs were used separately. The antitumor mechanism involved triggering ROS-dependent apoptosis as well as disruption of the mitochondrial membrane potential. Further studies showed that apoptosis by the Sal A and TNP combination was caspase-independent and that ERK, JNK and p38 of the serine/threonine MAPKs signaling pathway were involved in the cell death mechanism. Taken together, our data suggest that the combination of Sal A and TNP may be of therapeutic interest against colon cancer.
我们之前已经表明，从中东土生土长的植物 Centaurea ainetensis 和 Achillea falcata 中分别分离出的两种倍半萜内酯，salograviolide A（Sal A）和 iso-seco-tanapartholide（TNP），具有选择性抗肿瘤特性。在这里，我们旨在评估这两种化合物的单独作用及其组合的抗癌作用，研究它们生成活性氧（ROS）的潜力，并研究它们在人结肠癌细胞系中的潜在抗肿瘤机制。用 Sal A 和 TNP 单独或联合处理细胞，并监测细胞活力、细胞周期谱、细胞凋亡、ROS 生成和蛋白表达的变化。Sal A 和 TNP 联合使用时，HCT-116 和 DLD-1 细胞活力下降了 80%，而单独使用时则下降了 25%。抗肿瘤机制涉及触发依赖 ROS 的细胞凋亡以及线粒体膜电位的破坏。进一步的研究表明，Sal A 和 TNP 联合诱导的细胞凋亡与半胱天冬酶无关，并且丝氨酸/苏氨酸 MAPKs 信号通路中的 ERK、JNK 和 p38 参与了细胞死亡机制。总之，我们的数据表明，Sal A 和 TNP 的组合可能对结肠癌具有治疗意义。
