Cayman (–)-Securinine

(–)-Securinine is an alkaloid originally isolated from S. suffructicosa. It reduces proliferation of SW480 colon adenocarcinoma cells in a dose- and time-dependent manner via increased Beclin 1 expression and induction of autophagy. It decreases viability of HL-60 leukemia cells (IC₅₀s = 47.88, 23.85, and 18.87 μM at 24, 48, and 72 hours post-treatment, respectively). It also induces cell cycle arrest at the g₁/S phase and decreases PI3K, Akt, and mTOR gene expression in a dose-dependent manner. (–)-Securinine inhibits GABA and GABA-activated benzodiazepine binding to rat brain membranes (IC₅₀s = 57 and 101 μM, respectively). In vivo, (–)-securinine (5.2 mg/kg) induces clonic and tonic convulsions in mice, an effect that is reversed by administration of GABA.

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