Periplocin is a cardiac glycoside that has been isolated from P. sepium and has cardiac and anticancer activity. It increases viability and proliferation of mouse cardiac microvascular endothelial cells (CMECs) when used at concentrations ranging from 2 to 50 µM and improves left ventricular structure and function in a rat model of chronic heart failure. Periplocin inhibits cell proliferation in nine lung cancer cell lines in a time- and dose-dependent manner with IC50 values ranging from 0.12 to 53 µM. It induces apoptosis in SGC-7901 and MGC-803 gastric cancer cells and activates the ERK1/2-EGR1 pathway. Periplocin (5 and 20 mg/kg) reduces tumor growth in a hepatocellular carcinoma (HCC) mouse xenograft model. It also inhibits AKT and ERK autophosphorylation and tumor growth in an A549 lung cancer mouse xenograft model when administered at doses of 50 and 100 µg.