Apoptotic and anti-angiogenic effects of Pulsatilla koreana extract on hepatocellular carcinoma

Int J Oncol. 2012 Feb;40(2):452-60. doi: 10.3892/ijo.2011.1204. Epub 2011 Sep 20.


Chemoprevention through the use of food and plants has emerged as a novel approach to control various malignancies including cancer. Pulsatilla koreana extract (PKE) has been used to treat malaria and dysentery. The functions and effect of PKE in cancer treatment have been reported but with less information. In this study, we investigated the effect of PKE on the progression of hepatocellular carcinoma (HCC) cells and its mechanism. PKE strongly suppressed the growth of HCC cells in a dose-dependent manner. Apoptosis by PKE was observed by DAPI and TUNEL staining and accompanied with increases of cleaved PARP and caspase-3 in Huh-7 cells. Also, PKE decreased the expression of hypoxia-inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF), and inhibited tube formation and migration of human umbilical vein endothelial cells (HUVECs). In addition, PKE potently suppressed in vivo neovascularization in a mouse Matrigel plug assay. Furthermore, in vivo study showed that PKE significantly inhibited tumor growth in a mouse xenograft model, and induced apoptosis by increasing the cleaved PARP and caspase-3. The expressions of Ki-67, VEGF, and CD31 in the tumor tissue were decreased by the treatment of PKE. Taken together, our study demonstrates that PKE not only induced apoptosis but also inhibited cell growth and angiogenesis of human HCC. We suggest that PKE is an effective chemotherapeutic candidate for cancer therapy against HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Antineoplastic Agents, Phytogenic / urine
  • Apoptosis / drug effects
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Mice, Nude
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Plant Roots*
  • Pulsatilla*
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents, Phytogenic
  • Plant Extracts