Moreover, upregulation of death receptor (DR)-4 and -5, T-lymphoma invasion and metastasis (TIAM1), and Protease-activated receptor 4 (PAR4), as well as inhibition of DNA topoisomerase that are all mediated by the pro-apoptotic effects of cardiac glycosides, provide additional mechanisms which contribute in growth arrest of tumor cells [134]. This evidence concerns the gene F2RL3 and neoplasm.