Alpha-phellandrene-induced apoptosis in mice leukemia WEHI-3 cells in vitro

Environ Toxicol. 2016 Nov;31(11):1640-1651. doi: 10.1002/tox.22168. Epub 2015 Jul 15.


Although reports have shown that α-phellandrene (α-PA) is one of the monoterpenes and is often used in the food and perfume industry, our previous studies have indicated that α-PA promoted immune responses in normal mice in vivo. However, there is no available information to show that α-PA induced cell apoptosis in cancer cells, thus, we investigated the effects of α-PA on the cell morphology, viability, cell cycle distribution, and apoptosis in mice leukemia WEHI-3 cells in vitro. Results indicated that α-PA induced cell morphological changes and decreased viability, induced G0/G1 arrest and sub-G1 phase (apoptosis) in WEHI-3 cells. α-PA increased the productions of reactive oxygen species (ROS) and Ca2+ and decreased the levels of mitochondrial membrane potential (ΔΨm ) in dose- and time-dependent manners in WEHI-3 cells that were analyzed by flow cytometer. Results from confocal laser microscopic system examinations show that α-PA promoted the release of cytochrome c, AIF, and Endo G from mitochondria in WEHI-3 cells. These results are the first findings to provide new information for understanding the mechanisms by which α-PA induces cell cycle arrest and apoptosis in WEHI-3 cells in vitro. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1640-1651, 2016.

Keywords: WEHI-3 cells; apoptosis; cell cycle arrest; in vitro; α-phellandrene (α-PA).

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Caspases / metabolism
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cyclohexane Monoterpenes
  • Leukemia / drug therapy
  • Leukemia / pathology
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Monoterpenes / pharmacology*
  • Reactive Oxygen Species / metabolism


  • Cyclohexane Monoterpenes
  • Monoterpenes
  • Reactive Oxygen Species
  • alpha phellandrene
  • Caspases