Arenobufagin

Arenobufagin is a cardiotonic steroid that has been found in the skin secretions of the toad B. gargarizans and has anticancer activity.^1,2,3,4 It inhibits Na⁺/K⁺-ATPase activity in isolated guinea pig ventricular myocytes with an IC₅₀ value of 290 nM.¹ Arenobufagin (20-500 nM) induces cleavage of poly(ADP-ribose) polymerase (PARP), caspase-3, and caspase-9, as well as induces apoptosis in HepG2 hepatocellular carcinoma cells.² It inhibits proliferation of HepG2, Hep3B, BEL-7402, and MCF-7 cancer cells (IC₅₀s = 101.9, 39.8, 416.3, and 143.7 nM, respectively), as well as multidrug-resistant HepG2/adm and MCF-7/adr cancer cells (IC₅₀s = 730 and 67.5 nM, respectively). Arenobufagin (1 mg/kg once per day, i.v.) reduces tumor growth, the number and size of lung metastases, and tumor levels of the epithelial-to-mesenchymal transition (EMT) markers vimentin and β-catenin in a PC3 mouse xenograft model.³ Arenobufagin (5 and 10 ?M/plug) inhibits VEGF-induced angiogenesis in a Matrigel? plug assay in mice.⁴

1.dos Santos Cruz, J., and Matsuda, H.Arenobufagin, a compound in toad venom, blocks Na+-K+ pump current in cardiac myocytesEur. J. Pharmacol.239(1-3)223-226(1993) 2.Zhang, D.-M., Liu, J.-S., Deng, L.-J., et al.Arenobufagin, a natural bufadienolide from toad venom, induces apoptosis and autophagy in human hepatocellular carcinoma cells through inhibition of PI3K/Akt/ mTOR pathwayCarcinogenesis34(6)1331-1342(2013) 3.Chen, L., Mai, W., Chen, M., et al.Arenobufagin inhibits prostate cancer epithelial-mesenchymal transition and metastasis by down-regulating β-cateninPharmacol. Res.123130-142(2017) 4.Li, M.W., S., Liu, Z., Zhang, W., et al.Arenobufagin, a bufadienolide compound from toad venom, inhibits VEGF-mediated angiogenesis through suppression of VEGFR-2 signaling pathwayBiochem. Pharmacol.83(9)1251-1260(2012)