Involvement of p53, nuclear factor κB and Fas/Fas ligand in induction of apoptosis and cell cycle arrest by saikosaponin d in human hepatoma cell lines

In this study, we report the proapoptotic effect of saikosaponin d in two liver cancer cell lines, Hep G2 and Hep 3B cells. Treatment with saikosaponin d decreased the cell proliferation of Hep G2 and Hep 3B cells in a dose dependent manner. In Hep G2, saikosaponin d blocked the progression of cell cycle at G1 phase by inducing p53 expression and further up-regulating p21/WAF1 expression. In addition, 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. Furthermore, saikosaponin d also inhibited the cell survival signaling by enhancing the amount of IkappaBalpha in cytoplasm and reducing the level and activity of NF-kappaB in the nucleus, and subsequently attenuated the expression of Bcl-X-L in Hep G2 and Hep 3B cells. Saikosaponin d therefore decreased the cell proliferation and inducted apoptosis both in p53-postive Hep G2 and p53-negative Hep 3B cells. (C) 2004 Elsevier Ireland Ltd. All rights reserved.