Resveratrol at H igh D oses Acts as an Apoptotic Inducer in Endothelial Cells
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Abstract
Purposes: Resveratrol is a phenolic compound found in grapes and other food products. In order to assess the availability of resveratrol as an angio-inhibiting drug, we examined whether resveratrol plays an important role in bovine aortic endothelial cells (BAECs) for cell apoptosis and cell migration. Methods and Materials: Endothelial cell apoptosis was observed as detected by the Hoechst staining and the caspase-3 activity. Additionally, Western blotting was performed for monitoring the activities of various cell signaling molecules. Results: Resveratrol was shown to act as a pro-apoptotic agent. The pro-apoptotic effect of resveratrol was as great as that of etoposide, a well-known anti-cancer drug. In addition, resveratrol had an inhibitory effect on endothelial cell migration. The demonstrated efficacy of resveratrol suggests that resveratrol may be utilized as an anti-angiogenic drug. To determine the underlying mechanisms, we further investigated which signaling molecules are activated by resveratrol. Extracellular signal-regulated kinase (ERK) was activated by the treatment with resveratrol in BAECs, whereas endothelial nitric oxide synthetase (eNOS), Akt, and Jun N-terminal kinase (JNK) were inhibited. The pretreatment with PD compound, an ERK inhibitor, had no effect on the pro-apoptosis induced by resveratrol. Conclusion: Resveratrol plays an important role in endothelial cell apoptosis, indicating that resveratrol can be utilized as a potent anti-angiogenic drug. (Cancer Res Treat. 2006;38:48-53)
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