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

Abstract

D-limonene is a common monoterpene found in nature. Previously, it has been demonstratedthat 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 MAP38and ERK pathways. Limonene increased the NO levels by inducing cell apoptosis by two mechanisms:through the production of H2O2 and ERK pathway activation at low concentrations, andthrough 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 oxidativestress intermediates was involved.