Proteomic Analysis Reveals that Odoroside A Triggers G2/M Arrest and Apoptosis in Colorectal Carcinoma Through ROS-p53 Pathway

Proteomics. 2019 Aug;19(15):e1900092. doi: 10.1002/pmic.201900092. Epub 2019 Jul 18.

Abstract

Odoroside A (OA) is an active ingredient extracted from the leaves of Nerium oleander Linn. (Apocynaceae). This study aims to examine the anticancer bioactivity of OA against CRC cells and to investigate the action mechanisms involved. As a result, OA can significantly inhibit cellular ability and induce apoptosis of CRC cells in a concentration-dependent manner without any obvious cytotoxicity in normal colorectal epithelial cells. Then, quantitative proteomics combined with bioinformatics is adopted to investigate the alterations of proteins and signaling pathways in response to OA treatment. As suggested by the proteomic analysis, flow cytometry and Western blotting analyses validate that exposure of CRC cells to OA causes cell cycle arrest and apoptosis, accompanied with the activation of the ROS/p53 signaling pathway. This observation demonstrates that OA, as a natural product, can induce oxidative stress to suppress tumor cell growth, implicating a novel therapeutic agent against CRC without obvious side effects.

Keywords: ROS/p53 pathways; apoptosis; cell cycle; colorectal cancer; natural product; odoroside A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Cardenolides / pharmacology*
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Computational Biology
  • G2 Phase Cell Cycle Checkpoints / drug effects*
  • HT29 Cells
  • Humans
  • Proteomics / methods*
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / drug effects
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Cardenolides
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53
  • odoroside