Saikosaponin‑d inhibits proliferation of DU145 human prostate cancer cells by inducing apoptosis and arresting the cell cycle at G0/G1 phase

Mol Med Rep. 2014 Jul;10(1):365-72. doi: 10.3892/mmr.2014.2153. Epub 2014 Apr 15.

Abstract

Saikosaponin‑d (SSd), a triterpene saponin compound derived from Bupleurum radix, has been shown to have a cytotoxic effect on various cancer cell lines. However, its effect on prostate cancer cells has remained unexplored. The present study reports the apoptosis‑inducing effect of SSd on the DU145 human prostate carcinoma cell line. Treatment with SSd inhibited DU145 cell proliferation in a concentration‑dependent manner. Flow cytometric analysis showed that SSd inhibited the proliferation of DU145 cells by induction of apoptosis and cell cycle arrest at G0/G1 phase. Further mechanistic experiments demonstrated that SSd arrested the cell cycle at G0/G1 phase via upregulation of p53 and p21 and induced apoptosis by modulating B‑cell lymphoma 2 family proteins, dissipation of the mitochondrial membrane potential, release of cytochrome c into the cytosol and activation of caspase‑3. In conclusion the present study indicated that SSd induced apoptosis in DU145 cells by the intrinsic apoptotic pathway. Therefore, SSd may become a leading candidate drug for the therapy of prostate carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / toxicity*
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cytochromes c / metabolism
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / chemistry
  • Oleanolic Acid / toxicity
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Saponins / chemistry
  • Saponins / toxicity*
  • Tumor Suppressor Protein p53 / metabolism
  • Up-Regulation / drug effects
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Cyclin-Dependent Kinase Inhibitor p21
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Saponins
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Oleanolic Acid
  • Cytochromes c
  • Caspase 3
  • saikosaponin D