STK214947, a novel indole alkaloids, inhibits HeLa and SK-HEP-1 cells survival and EMT process by bloking the Notch3 and Akt signals

Abstract

Apoptosis and epithelial-to-mesenchymal transition (EMT) are closely associated with tumor survival and metastasis. These are the basic events in tumor occurrence and progression. STK214947 is an indole alkaloid with a skeleton that is similar to that of indirubin. Indole alkaloids have attracted considerable attention because of their antitumor activity. However, the relationship between STK214947 and these basic events remains unknown. In this study, the effects of STK214947 on inducing apoptosis and reversing the EMT process in tumor cells were confirmed. Mild concentrations of STK214947 inhibited tumor cell migration by reversing EMT and significantly regulated the expression of EMT-related proteins, including Notch3, E-cadherin, N-cadherin and vimentin. In addition, STK214947 in high concentration could induce apoptosis by down-regulating Notch3, p-Akt/Akt, and NF-κB, and upregulating Caspase 3. These findings support the further development of STK214947 as a potential antitumor small molecule that targets Notch3 and Akt signal transduction in cancer.