Narciclasine

Narciclasine is a plant growth modulator. Narciclasine modulates the Rho/Rho kinase/LIM kinase/cofilin signaling pathway, greatly increasing GTPase RhoA activity as well as inducing actin stress fiber formation in a RhoA-dependent manner. IC50 & Target:Rho^[1] In Vitro: Narciclasine activates Rho and stress fibers in glioblastoma multiforme cells. The mean IC₅₀ of ~50 nM calculated on the 6 human glioblastoma multiforme (U373, Hs683, GL19, GL5, GL16, GL17), The mean IC₅₀ value of 47 nM for Narciclasine across a panel of 60 cancer cell lines^[1]. Bioassay-guided fractionation of the A. belladonna extract resulted in the identification of lycorine as the bio-active compound. The IC₅₀ measured for radicle growth inhibition is 0.1 μM for Narciclasine^[2]. In Vivo: The i.v. regimen of Narciclasine at 1 mg/kg significantly (P=0.02) increases the survival of GL19 glioblastoma multiforme-bearing mice. Narciclasine when given orally at the same dose five times a week for 5 consecutive weeks also significantly increases animal survival in this model (P=0.008). Oral treatment with Narciclasine at 1 mg/kg significantly increases the survival (P=0.004) of Hs683 glioblastoma multiforme-bearing mice. Increasing the number of doses administered per week does not increase the survival of these Hs683 glioblastoma multiforme-bearing mice. Narciclasine appears to show similar increased survival in these models to temozolomide but at appreciable lower doses and following both oral and i.v. administration^[1].