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 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 H₂O₂ and ERK pathway activation at low concentrations, and through the inhibition of farnesylation of proteins and O₂− production at high concentrations. Both mechanisms were related to the increase in total nitrites, and the production of oxidative stress intermediates was involved.

Keywords: :

• Lymphoma
• Limonene
• Oxidative stress
• Nitric oxide

ACKNOWLEDGMENT

This work was supported with PIP 5232 from CONICET and Project no. 9601 of the National University of San Luis, Argentina.