Alkaloids from Beach Spider Lily (Hymenocallis littoralis) Induce Apoptosis of HepG-2 Cells by the Fas-signaling Pathway

Abstract

Alkaloids are the most extensively featured compounds of natural anti-tumor herbs, which have attracted muchattention in pharmaceutical research. In our previous studies, a mixture of major three alkaloid components (5,6-dihydrobicolorine, 7-deoxy-trans-dihydronarciclasine, littoraline) from Hymenocallis littoralis were extracted,analyzed and designated as AHL. In this paper, AHL extracts were added to human liver hepatocellular cellsHepG-2, human gastric cancer cell SGC-7901, human breast adenocarcinoma cell MCF-7 and human umbilicalvein endothelial cell EVC-304, to screen one or more AHL-sensitive tumor cell. Among these cells, HepG-2 wasthe most sensitive to AHL treatment, a very low dose (0.8μg/ml) significantly inhibiting proliferation . The nontumorcell EVC-304, however, was not apparently affected. Effect of AHL on HepG-2 cells was then explored.We found that the AHL could cause HepG-2 cycle arrest at G2/M checkpoint, induce apoptosis, and interruptpolymerization of microtubules. In addition, expression of two cell cycle-regulated proteins, CyclinB1 and CDK1,was up-regulated upon AHL treatment. Up-regulation of the Fas, Fas ligand, Caspase-8 and Caspase-3 wasobserved as well, which might imply roles for the Fas/FsaL signaling pathway in the AHL-induced apoptosis ofHepG-2 cells.