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.
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.
Manuele
Maria Gabriela
MG
IQUIMEFA-CONICET, Buenos Aires, Argentina.
Barreiro Arcos
Maria Laura
ML
Davicino
Roberto
R
Ferraro
Graciela
G
Cremaschi
Graciela
G
Anesini
Claudia
C
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D053138:Cyclohexenes / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D000077222:Limonene; D008223:Lymphoma / Q000378:metabolism* / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology*; D000097782:NF-kappaB-Inducing Kinase
D000970:Antineoplastic Agents; D053138:Cyclohexenes; D006861:Hydrogen Peroxide; D000077222:Limonene; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D017346:Protein Serine-Threonine Kinases; D013481:Superoxides; D013729:Terpenes; D000097782:NF-kappaB-Inducing Kinase