Phaseoloideside E, a Novel Natural Triterpenoid Saponin Identified From Entada phaseoloides, Induces Apoptosis in Ec-109 Esophageal Cancer Cells Through Reactive Oxygen Species Generation

Abstract

Phaseoloideside E (PE), a new oleanane-type triterpene saponin, was isolated from the seed kernels of Entada phaseoloides (Linn.) Merr. PE had strong cytotoxic activity against an array of malignant cells. Typical morphological and biochemical features of apoptosis were observed in PE-treated Ec-109 cells. PE induced a dose-dependent increase in the sub-G1 fraction of the cell cycle and DNA fragmentation. Decreases in the mitochondrial membrane potential, SOD activity, and GSH content were also observed. Further investigations revealed that PE reduced the ratio of Bcl-2 to Bax and increased the activities of caspase-3 and -9, but this was prevented by Z-VAD-fmk. PE also induced a decrease of the sub-G1 fraction. Furthermore, PE-induced apoptosis was mediated by up-regulating cellular ROS, which was suppressed by cotreating the cells with N-acetylcysteine (NAC). NAC also attenuated the ratio of sub-G1, the generation of DNA fragmentation and the expression of Bcl-2, Bax, caspase-3, and caspase-9. Interestingly, PE did not up-regulate ROS or induce cell death in untransformed cells. These data showed that PE induces cell death through up-regulation of cellular ROS production. Our investigation provides the scientific basis for the traditional application of this herb and suggests the possibility that PE may be used for a treatment of esophageal carcinoma. [Supplementary materials: available only at http://dx.doi.org/10.1254/jphs.12193FP].