Scandenolone, a natural isoflavone derivative from Cudrania tricuspidata fruit, targets EGFR to induce apoptosis and block autophagy flux in human melanoma cells

Natural isoflavones have been reported to have a potential of antineoplastic activity. However, novel and specific isoflavones are still needed to be explored, and the underlying molecular mechanisms and the intracellular targets of these compounds remain elusive. In our study, we discovered that scandenolone, a natural isoflavonoid derivative from Cudrania tricuspidata fruit, exhibited antineoplastic activity in SK-MEL-28 cells by inducing intrinsic apoptosis and blocking autophagy flux. In addition, scandenolone significantly induced G2/M cycle arrest and inhibited cell migration. The study of the intracellular molecular targets showed that scandenolone binds directly to the active kinase and ATP-binding site of EGFR, which results in downregulating the AKT/mTOR/ERK signaling pathway. Therefore, out results indicate that scandenolone from Cudrania tricuspidata fruit, significantly sensitized SK-MEL-28 cells to apoptosis and repressed the proliferation of the cells, which showed an enormous potential to treat melanoma.