Resveratrol induces apoptosis via ROS-triggered autophagy in human colon cancer cells

Int J Oncol. 2012 Apr;40(4):1020-8. doi: 10.3892/ijo.2012.1325. Epub 2012 Jan 3.


Resveratrol (Res; 3,4',5-trihydroxy-trans-stilbene), which is a polyphenol found in grapes, can block cell proliferation and induce growth arrest and/or cell death in several types of cancer cells. However, the precise mechanisms by which Res exerts anticancer effects remain poorly understood. Res blocked both anchorage-dependent and -independent growth of HT-29 and COLO 201 human colon cancer cells in a dose- and time-dependent manner. Annexin V staining and Western blot analysis revealed that Res induced apoptosis accompanied by an increase in Caspase-8 and Caspase-3 cleavage. In HT-29 cells, Res caused autophagy as characterized by the appearance of autophagic vacuoles by electron microscopy and elevation of microtubule-associated protein 1 light chain 3 (LC3)-II by immunoblotting, which was associated with the punctuate pattern of LC3 detected by fluorescein microscopy. Inhibition of Res-induced autophagy by the autophagy inhibitor 3-methyladenine caused a significant decrease in apoptosis accompanied by decreased cleavage of Casapse-8 and Caspase-3, indicating that Res-induced autophagy was cytotoxic. However, inhibition of Res-induced apoptosis by the pan-caspase inhibitor Z-VAD(OMe)-FMK did not decrease autophagy but elevated LC3-II levels. Interestingly, Res increased the intracellular reactive oxygen species (ROS) level, which correlated to the induction of Casapse-8 and Caspase-3 cleavage and the elevation of LC3-II; treatment with ROS scavenger N-acetyl cysteine diminished this effect. Therefore, the effect of Res on the induction of apoptosis via autophagy is mediated through ROS in human colon cancer cells.

MeSH terms

  • Anticarcinogenic Agents / pharmacology
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects*
  • Autophagy / drug effects
  • Caspase 3 / metabolism
  • Caspase 8 / metabolism
  • Cell Growth Processes / drug effects
  • Cell Line, Tumor
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • HT29 Cells
  • Humans
  • Oligopeptides / pharmacology
  • Reactive Oxygen Species / metabolism*
  • Resveratrol
  • Signal Transduction / drug effects
  • Stilbenes / pharmacology*


  • Anticarcinogenic Agents
  • Antineoplastic Agents, Phytogenic
  • Oligopeptides
  • Reactive Oxygen Species
  • Stilbenes
  • benzyloxycarbonyl-valyl-alanyl-aspartic acid
  • Caspase 3
  • Caspase 8
  • Resveratrol