Antiproliferation and apoptosis induced by evodiamine in human colorectal carcinoma cells (COLO-205)

Chem Biodivers. 2009 Jun;6(6):924-33. doi: 10.1002/cbdv.200800256.

Abstract

Evodiamine (1), a biologically active alkaloid isolated from Evodia rutaecarpa (known in Chinese as Wu-Chu-Yu), has antioxidant, anti-inflammatory, and anticancer activities. It has recently been demonstrated that the cytotoxic activities of 1 might be due to its ability to inhibit cell growth and induce apoptosis. In this study, we investigated the effects of 1 on growth and apoptosis in COLO-205 cells by MTT assay, fluorescence microscopy, transmission electron microscopy, DNA fragmentation assay, flow cytometry, immunohistochemical analysis, Western blotting, and caspase-3 activity assay. Our data revealed that 1 could significantly inhibit COLO-205 cell proliferation in a dose-dependent manner, and 1-treated COLO-205 cells displayed typical morphological apoptotic characteristics and formation of DNA ladders in agarose gel electrophoresis. The COLO-205 cell cycle was arrested in G(2)/M phase by 1. Meanwhile, 1 increased the expression of Bax and p53, decreased the expression of Bcl-2, lowered the mitochondrial transmembrane potential, and induced the activation of caspase-3. These activities may contribute to the anticarcinogenic action of 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticarcinogenic Agents / chemistry
  • Anticarcinogenic Agents / isolation & purification
  • Anticarcinogenic Agents / toxicity*
  • Apoptosis*
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Caspase 3 / metabolism
  • Cell Cycle
  • Cell Proliferation
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Evodia / chemistry
  • G2 Phase
  • Humans
  • Membrane Potentials
  • Mitochondria / drug effects
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / toxicity*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Quinazolines / chemistry
  • Quinazolines / isolation & purification
  • Quinazolines / toxicity*
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • Anticarcinogenic Agents
  • Plant Extracts
  • Proto-Oncogene Proteins c-bcl-2
  • Quinazolines
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • evodiamine
  • Caspase 3