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Research ArticleCELLULAR AND MOLECULAR

Perturbation by Geraniol of Cell Membrane Permeability and Signal Transduction Pathways in Human Colon Cancer Cells

S. Carnesecchi, A. Bradaia, B. Fischer, D. Coelho, M. Schöller-Guinard, F. Gosse and F. Raul
Journal of Pharmacology and Experimental Therapeutics November 2002, 303 (2) 711-715; DOI: https://doi.org/10.1124/jpet.102.039263
S. Carnesecchi
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A. Bradaia
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B. Fischer
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D. Coelho
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M. Schöller-Guinard
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F. Gosse
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F. Raul
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Abstract

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.

Footnotes

  • This work was supported by a grant from Association pour la Recherche sur le Cancer (ARC).

  • DOI: 10.1124/jpet.102.039263

  • Abbreviations:
    MVA
    mevalonate
    HMG
    3-hydroxy-3-methylglutaryl
    PKC
    protein kinase C
    ERK
    extracellular signal-regulated kinase
    DMEM
    Dulbecco's modified Eagle's medium
    MAPK
    mitogen-activated kinases
    • Received May 28, 2002.
    • Accepted July 8, 2002.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 303 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 303, Issue 2
1 Nov 2002
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Research ArticleCELLULAR AND MOLECULAR

Perturbation by Geraniol of Cell Membrane Permeability and Signal Transduction Pathways in Human Colon Cancer Cells

S. Carnesecchi, A. Bradaia, B. Fischer, D. Coelho, M. Schöller-Guinard, F. Gosse and F. Raul
Journal of Pharmacology and Experimental Therapeutics November 1, 2002, 303 (2) 711-715; DOI: https://doi.org/10.1124/jpet.102.039263

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Research ArticleCELLULAR AND MOLECULAR

Perturbation by Geraniol of Cell Membrane Permeability and Signal Transduction Pathways in Human Colon Cancer Cells

S. Carnesecchi, A. Bradaia, B. Fischer, D. Coelho, M. Schöller-Guinard, F. Gosse and F. Raul
Journal of Pharmacology and Experimental Therapeutics November 1, 2002, 303 (2) 711-715; DOI: https://doi.org/10.1124/jpet.102.039263
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