Cananginone Abrogates EMT in Breast Cancer Cells through Hedgehog Signaling

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.