Linalool preferentially induces robust apoptosis of a variety of leukemia cells via upregulating p53 and cyclin-dependent kinase inhibitors

Toxicology. 2010 Jan 31;268(1-2):19-24. doi: 10.1016/j.tox.2009.11.013. Epub 2009 Nov 14.

Abstract

Linalool, a natural small molecule monoterpene, has been shown to have anti-tumor activity against several human tumor cell lines in vitro; however, the anti-leukemia spectrum and molecular mechanisms inhibiting tumor cell growth are not fully understood. In the present study, we demonstrated that linalool preferentially induced growth arrest and apoptosis of a variety of human leukemia cells, but spared normal hematopoietic cells. Treatment of leukemia cells by linalool for 12h led to strong activation of p53, cyclin-dependent kinase inhibitors (CDKIs), GADD45alpha, c-jun and phosphorylated-JNK, suggesting that linalool-induced apoptosis might be associated with activation of p53 and CDKIs. The findings here warrant further investigation of this class of natural product as lead compound for developing novel therapeutic agents for leukemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclic Monoterpenes
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Humans
  • Monoterpenes / pharmacology*
  • Protein Kinase Inhibitors / pharmacology*
  • Tumor Suppressor Protein p53 / metabolism*
  • Up-Regulation / drug effects*

Substances

  • Acyclic Monoterpenes
  • Monoterpenes
  • Protein Kinase Inhibitors
  • Tumor Suppressor Protein p53
  • linalool
  • Cyclin-Dependent Kinases