ANTIPROLIFERATIVE ACTION OF LIMONENE ON A LYMPHOMA CELL LINE: RELATION BETWEEN NITRIC OXIDE AND REACTIVE SPECIES OF OXYGEN.

PATRICIA MICUCCI; ROBERTO DAVICINO; GRACIELA FERRARO; CLAUDIA ANESINI

Rosario, Santa Fe, Argentina

Congreso; XLI reunion anual de la sociedad Argentina de farmacología experimental; 2009

Sociedad Argentina de Farmacología Experimental

Limonene (L) exerts antiproliferative effect on a lymphoma cell line (BW5147) increasing nitric oxide (NO). H2O2 is related to cell proliferation and NO modulation. The aim of the study was to analyze the participation of H2O2 and superoxide anion (O2.-) in the effect of limonene. The enzymes involve in H2O2 modulation such as catalase (CAT), superoxide dismutase (SOD) and peroxidase (Px) were studied by a spectroscopy assay. Results were expressed as Mean ± SEM of three experiments made by triplicate: &P<0.05 (respect to L) * P<0.05 (Respect to Basal) (Student ´s t test). H2O2 (mM/106 cells): Basal: 0.0578 ±  0.0088; L 40 µg/ml: 0.085 ±  0.005 *, L 100 µg/ml: 0.0580± 0.004, L 40 µg/ml +MEK 1/2 inhibitor: 0.055 ± 0.0050&, L 100 µg/ml+ MEK ½ inhibitor: 0.056± 0.005. O2.- (nmol of  reduced NBT /106 cells): Basal: 21.53± 0.054, L 100 µg/ml: 27.11 ± 0.52 **, L 100 µg/ml + mevalonic acid: 18.08 ± 1.49 &. SOD activity (U/ml/ 106 cells): Basal: 0.66 ± 0.060, L 40 µg/ml: 0.77± 0.075*, L 100 µg/ml: 0.20± 0.02**. PER activity (U/ml/106 cells): 3x10-4 ± 5x10-5, L 40 µg/ml: 1.3x10-4 ± 1x10-5**, L 100 µg/ml: 1.5x10-4 ± 2x10-5**. At low concentration, L via ERK increased H2O2 level by SOD activation and inhibition of Px. At high concentration, L increased O2.- by inhibition of farnesylation and SOD inhibition. Oxidative stress is implicated in L antiproliferative action.