School of Applied and Interdisciplinary Sciences, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, 700032, India.
School of Chemical Sciences, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, 700032, India.
Chem Biodivers. 2022 May;19(5):e202100823. doi: 10.1002/cbdv.202100823. Epub 2022 Mar 29.
Cananginones, a family of linear acetogenins found as secondary metabolites in the plant kingdom, show cytotoxicity against several types of cancer cells. We aimed to investigate the efficacy of cananginone and its mechanism as an anti-cancer agent. Our initial screening of Cananginone against HepG2, PC3, A549, and MCF7 cells showed anti-cancer activities and is more potent against MCF7 cells, consistent with the previous report. Next, cell-based assays have revealed that cananginone abrogates cancer stem cell renewal as well as Epithelial-Mesenchymal Transition (EMT) and increased the ROS level beyond the threshold level thus reducing the viability of cancer cells. In the connection of Hh-Gli to EMT, our study indicated that cananginone inhibits Gli1 in a non-canonical pathway. Presumably, this is the first report on the inhibitory activity of cananginone in the Hh pathway and is different from Hh-antagonists cyclopamine and GANT 61 considering the mechanism.
Cananginones 是植物界中发现的一类线性乙酰氧基醇类化合物，作为次级代谢产物具有细胞毒性，可抑制多种类型的癌细胞。我们旨在研究 Cananginone 的抗癌功效及其作用机制。我们最初对 HepG2、PC3、A549 和 MCF7 细胞进行 Cananginone 筛选，结果显示其具有抗癌活性，且对 MCF7 细胞的作用更强，这与之前的报道一致。随后，细胞实验表明，Cananginone 可阻断肿瘤干细胞更新及上皮-间充质转化（EMT），并使 ROS 水平升高超过阈值，从而降低癌细胞的活力。在 Hh-Gli 与 EMT 的关联中，我们的研究表明，Cananginone 可在非经典途径中抑制 Gli1。可以推测，这是首次报道 Cananginone 对 Hh 通路具有抑制活性，与 Hh 拮抗剂 cyclopamine 和 GANT 61 不同，考虑到其作用机制。
