(–)-Securinine

(–)-Securinine is an alkaloid originally isolated from S. suffructicosa.¹ It reduces proliferation of SW480 colon adenocarcinoma cells in a dose- and time-dependent manner via increased Beclin 1 expression and induction of autophagy.² 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).³ 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).¹ In vivo, (–)-securinine (5.2 mg/kg) induces clonic and tonic convulsions in mice, an effect that is reversed by administration of GABA.⁴

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1. Beutler, J.A., Karbon, E.W., Brubaker, A.N., et al. Securinine alkaloids: A new class of GABA receptor antagonist. Brain Res. 330(1), 135-140 (1985).

2. Xia, Y.-H., Chang, C.-R., Yao, S.-Y., et al. L-securinine induced the human colon cancer SW480 cell autophagy and its molecular mechanism. Fitoterapia 82(8), 1258-1264 (2011).

3. Han, S., Zhang, G., Li, M., et al. L-securinine induces apoptosis in the human promyelocytic leukemia cell line HL-60 and influences the expression of genes involved in the PI3K/AKT/mTOR signaling pathway. Oncol. Rep. 31(5), 2245-2251 (2014).

4. Tao, S.-C., Peng, J.-Z., and Lu, M.-W. Central convulsive action of l-securinine. Zhongguo Yao Li Xue Bao. 7(1), 9-12 (1986).