Saikosaponin D is a saponin extract derived from several species of Bupleurum (Umbelliferae), which is used for the treatment of various liver diseases in traditional Chinese medicine. In this study, we report that Saikosaponin D inhibits the cell growth of human lung cancer cell line A549 and provide a molecular understanding of this effect. The results showed that Saikosaponin D inhibited the proliferation of A549 by inducing apoptosis and blocking cell cycle progression in the G1 phase. ELISA assay showed that Saikosaponin D significantly increased the expression of p53 and p21/WAF1 protein, contributing to cell cycle arrest. An enhancement in Fas/APO-1 and its two form ligands, membrane-bound Fas ligand (mFasL) and soluble Fas ligand (sFasL), as well as Bax protein, was responsible for the apoptotic effect induced by Saikosaponin D. Taken together, our study suggests that the induction of p53 and activity of the Fas/FasL apoptotic system may participate in the antiproliferative activity of Saikosaponin D in A549 cells. © 2004 Elsevier Inc. All rights reserved.
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