Securinine

(-) -Securinine is plant-derived alkaloid and also a GABAA receptor antagonist. (In Vitro) : (-) -Securinine is a major plant-derived alkaloid and also a GABAA receptor antagonist. (-) -Securinine is significantly potent on HeLa cells growth inhibition with IC50 values of 7.02±0.52 μg/mL (32.3 μM) . (-) -Securinine induces apoptosis in a dose-dependent manner in the tested cells, increases the percentage of ROS positive cells and depolarized cells as well as stimulates the activity of ERK1/2, caspase-9 and -3/7. (-) -Securinine also induces cell cycle arrest in S phase. Real-time PCR analysis shows high expression of tumor necrosis factor receptor superfamily (TNFRSF) genes in the cells stimulated with (-) -Securinine. (In Vivo) :In this tumor model, tumor growth is significantly impaired with (-) -Securinine treatment indicating that (-) -Securinine has potential as an Acute Myeloid Leukemia (AML) therapeutic. (-) -Securinine treated mice (n=5 mice, bilateral tumors), exhibit an average of more than 75% smaller tumors than vehicle treated mice at the end of the study period.