Veratramine

The hedgehog (Hh) signaling pathway, which is blocked by cyclopamine , plays a key role in morphogenesis and has potential applications in the treatment of cancer.^1,2,3 Veratramine, a teratogenic steroidal alkaloid isolated from the corn lily (Veratrum sp.), is an analog of cyclopamine that can inhibit the Hh signaling-dependent proliferation of NIH/3T3 cells at 8 μM.⁴ Additionally, veratramine has anti-thrombotic activity as it dose dependently inhibits platelet aggregation in rabbits ex vivo. While it may be most useful as a signal transduction inhibitor for treating tumors, veratramine also induces serotonin release and inhibits its re-uptake in the CNS.^5,6

1.Heretsch, P., Tzagkaroulaki, L., and Giannis, A.Cyclopamine and hedgehog signaling: Chemistry, biology, medical perspectivesAgnew. Chem. Int. Ed. Engl.49(20)3418-3427(2010) 2.Xu, F.G., Ma, Q.Y., and Wang, Z.Blockade of hedgehog signaling pathway as a therapeutic strategy for pancreatic cancerCancer Lett.283(2)119-124(2009) 3.Mahindroo, N., Punchihewa, C., and Fujii, N.Hedgehog-Gli signaling pathway inhibitors as anticancer agentsJ. Med. Chem.52(13)3829-3845(2009) 4.Tang, J., Li, H.L., Shen, Y.H., et al.Antitumor and antiplatelet activity of alkaloids from Veratrum dahuricumPhytother. Res.24(6)821-826(2010) 5.Nagata, R., Izumi, K., Iwata, S.i., et al.Mechanisms of veratramine-induced 5-HT syndrome in miceJpn. J. Pharmacol.55139-146(1991) 6.Fukuma, K.Actions of veratramine on the central nervous systemJpn. J. Pharmacol.5102-114(1956)