Limonene exerts antiproliferative effects and increases nitric oxide levels on a lymphoma cell line by dual mechanism of the ERK pathway: relationship with oxidative stress

Cancer Invest. 2010 Feb;28(2):135-45. doi: 10.3109/07357900903179583.


D-limonene is a common monoterpene found in nature. Previously, it has been demonstrated that it has antiproliferative effects on a lymphoma cell line by increasing the nitric oxide (NO) level. In the present work this mechanism is analyzed by evaluating the participation of MAP38 and ERK pathways. Limonene increased the NO levels by inducing cell apoptosis by two mechanisms: through the production of H(2)O(2) and ERK pathway activation at low concentrations, and through the inhibition of farnesylation of proteins and O(2)- production at high concentrations. Both mechanisms were related to the increase in total nitrites, and the production of oxidative stress intermediates was involved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cyclohexenes / pharmacology*
  • Humans
  • Hydrogen Peroxide / metabolism
  • Limonene
  • Lymphoma / metabolism*
  • Lymphoma / pathology*
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type II / metabolism
  • Oxidative Stress* / physiology
  • Protein-Serine-Threonine Kinases / metabolism
  • Signal Transduction
  • Superoxides / metabolism
  • Terpenes / pharmacology*


  • Antineoplastic Agents
  • Cyclohexenes
  • Terpenes
  • Superoxides
  • Nitric Oxide
  • Limonene
  • Hydrogen Peroxide
  • Nitric Oxide Synthase Type II
  • Protein-Serine-Threonine Kinases
  • NF-kappa B kinase