Induction of mitochondria-mediated apoptosis in human gastric adenocarcinoma SGC-7901 cells by kuraridin and Nor-kurarinone isolated from Sophora flavescens

Asian Pac J Cancer Prev. 2011;12(10):2499-504.

Abstract

The study was designed as one of a series to find novel anticancer compounds from Chinese herbs. For this purpose, we screened an ethanol extract of 300 herbs against SGC-7901 cells. Sophora flavescen was included in those showing potential cytotoxic activity. Target compounds were therefore isolated and analyzed on analytical HPLC. Chromatography showed only one peak with a purity of 97%. The ESI-MS spectrum showed two molecular ions: m/z 424(M+) and 438(M+). Furthermore, combining the data of 1HNMR and 13CNMR, it was deduced that this product was a mixture of two compounds; kuraridin (1) and nor-kurarinone (2). The concentration was [1]:[2]=9:10, the chemical structural formulae are C25H28O6 and C26H30O6. In this study, mechanisms involved by the mixture of compounds 1 and 2-induced growth inhibition including apoptosis and G2/M phase arrest in human gastric adenocarcinoma SGC-7901 cells were examined for the first time. Triggering of the mitochondrial apoptotic pathway was demonstrated by loss of mitochondrial membrane potential, reduction in the Bcl-2/Bax ratio, and significant activation and cleavage of caspase-3. Additionally, the production of reactive oxygen species (ROS) was also increased. Taken together, our results indicated that the cytotoxic efficacy of the mixture of compounds 1 and 2 is mainly due to induction of cell cycle arrest and apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chalcones / pharmacology*
  • Flavonoids / pharmacology*
  • G2 Phase Cell Cycle Checkpoints
  • Humans
  • Medicine, Chinese Traditional
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / metabolism
  • Monoterpenes / pharmacology*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Sophora / chemistry*
  • Stomach Neoplasms / metabolism*
  • bcl-2-Associated X Protein / metabolism

Substances

  • Chalcones
  • Flavonoids
  • Monoterpenes
  • Plant Extracts
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • kuraridin
  • kurarinone
  • Caspase 3