RT Journal Article
SR Electronic
T1 Perturbation by Geraniol of Cell Membrane Permeability and Signal Transduction Pathways in Human Colon Cancer Cells
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 711
OP 715
DO 10.1124/jpet.102.039263
VO 303
IS 2
A1 S. Carnesecchi
A1 A. Bradaia
A1 B. Fischer
A1 D. Coelho
A1 M. Schöller-Guinard
A1 F. Gosse
A1 F. Raul
YR 2002
UL http://jpet.aspetjournals.org/content/303/2/711.abstract
AB Geraniol, a natural component of plant essential oils, has antiproliferative effects on human colon cancer cells. To obtain more insight into its mechanism of action, we studied its effect on the resting membrane potential and on the expression of proteins involved in cell signaling pathways. Since geraniol is a well known inhibitor of mevalonate metabolism, the effect of mevalonate supplementation on geraniol-triggered growth inhibition was also determined. Geraniol (400 μM) induced membrane depolarization with a decrease of membrane resistance due to local perforation of the cell membrane. Incubation of Caco-2 cells with geraniol (400 μM) for 6 h caused a 60% reduction of protein kinase C (PKC) activity. After 16 h of incubation, geraniol decreased by 50% the amount of active forms of p44/p42 extracellular signal-regulated protein kinases (ERK). Mevalonate supplementation did not reverse inhibition of cell growth by geraniol. These results indicate that the antiproliferative effect of geraniol on Caco-2 cells was not related to a limitation of the mevalonate pool but was directly linked to the perturbation of cell membrane function leading to the reduction of PKC activity and to the decreased expression of p44/p42 ERK active forms. The American Society for Pharmacology and Experimental Therapeutics