Perturbation by geraniol of cell membrane permeability and signal transduction pathways in human colon cancer cells
Perturbation by geraniol of cell membrane permeability and signal transduction pathways in human colon cancer cells
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DOI：
10.1124/jpet.102.039263
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发表时间：
2002-11-01
影响因子：
3.5
通讯作者：
Raul, F
中科院分区：
文献类型：
--
作者：
Carnesecchi, S;Bradaia, A;Raul, F
香叶醇是植物精油的天然成分，对人结肠癌细胞具有抗增殖作用。为了更深入地了解其作用机制，我们研究了其对静息膜电位和参与细胞信号传导途径的蛋白质表达的影响。由于香叶醇是一种众所周知的甲羟戊酸代谢抑制剂，因此还测定了甲羟戊酸补充对香叶醇触发的生长抑制的影响。香叶醇（400 μ M）诱导的膜去极化与膜电阻的降低，由于局部穿孔的细胞膜。用香叶醇（400 μ M）孵育Caco-2细胞6小时，可使蛋白激酶C（PKC）活性降低60%。孵育16小时后，香叶醇减少了50%的p44/p42细胞外信号调节蛋白激酶（ERK）的活性形式的量。甲羟戊酸补充剂没有逆转香叶醇对细胞生长的抑制作用。这些结果表明香叶醇对Caco-2细胞的抗增殖作用与甲羟戊酸库的限制无关，但与细胞膜功能的扰动直接相关，导致PKC活性降低和p44/p42 ERK活性形式的表达降低。
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 muM) 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 muM) 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.