Neriifolin, a CNS-penetrating cardiac glycoside, is an inhibitor of the Na+, K+-ATPase. Neriifolin can target beclin 1, inhibits the formation of LC3-associated phagosomes and ameliorates experimental autoimmune encephalomyelitis (EAE) development. Neriifolin induces cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells[1][2.
Neriifolin (0.1μg/mL; 48 hours) induces apoptosis in HepG2 cells. Neriifolin (0-8 μg/mL; 72 hours) reduces viability of HepG2 cells. Neriifolin also induces S and G2/M phase arrests of the cell cycle and stimulates apoptosis of HepG2 cells. Stimulation of HepG2 cells with Neriifolin induced activation of caspase-3, -8, and -9, and up-regulated expression of Fas and FasL proteins[1].
[1]. Keller CW, et al. ATG-dependent phagocytosis in dendritic cells drives myelin-specific CD4+ T cell pathogenicity during CNS inflammation. Proc Natl Acad Sci U S A. 2017;114(52):E11228-E11237. [2]. Zhao Q, et al. Neriifolin from seeds of Cerbera manghas L. induces cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells. Fitoterapia. 2011;82(5):735-741.