Perturbation by geraniol of cell membrane permeability and signal transduction pathways in human colon cancer cells.
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 microM) 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 microM) 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.
Carnesecchi
S
S
Laboratory of Nutritional Oncology, Institut National de la Santé et de la Recherche Médicale, Strasbourg, France.
Bradaia
A
A
Fischer
B
B
Coelho
D
D
Schöller-Guinard
M
M
Gosse
F
F
Raul
F
F
D000080462:Acyclic Monoterpenes; D015153:Blotting, Western; D018938:Caco-2 Cells; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004594:Electrophysiology; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008798:Mevalonic Acid / Q000494:pharmacology; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D013729:Terpenes / Q000494:pharmacology*
D000080462:Acyclic Monoterpenes; D013729:Terpenes; D011493:Protein Kinase C; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C007836:geraniol; D008798:Mevalonic Acid