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KMID : 0613820040140050800
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Journal of Life Science
2004 Volume.14 No. 5 p.800 ~ p.808
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Induction of Cdk inhibitor p21 and inhibition of cyclooxygenase-2 by resveratrol in human lung carcinoma A549 cells
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Kim Young-Ae
Lim Sun-Young
Lee Suk-Hee
Park Kun-Young
Lee Won-Ho
Choi Yung-Hyun
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Abstract
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Resveratrol, a phytoalexin found at high levels in grapes and in grape products such as red wine, has been reported to possess a wide range of biological and pharmacological activities including anti- oxident, anti-inflammatory, anti-mutagenic, and anti-carcinogenic effects. According to recent studies, this compound is an effective inhibitor of cell growth in general, triggers partial arrest of the cell cycle and induce apoptosis. In this study, the anti-proliferative effects of resveratrol in A549 human lung carcinoma cells were investigated. It is shown that resveratrol induced the growth inhibition in a time-dependent manner and morphological changes of A549 cells, which were associated with induction of S phase arrest of the cell cycle and apoptotic cell death. The Bcl-XL levels were markedly down-regulated in resveratrol treated cells, however, Bax and Bcl-2 were remained unchanged. Resveratrol treatment induced the proteolytic degradation of Sp-1 and proliferating cell nuclear antigen protein, and inhibited the expression of β-catenin protein. Resveratrol treatment also induced a marked up-regulation of cyclin-dependent kinase (Cdk) inhibitor p21 and inhibited the kinase activities of Cdk2 and Cdk4. In addition, resveratrol treatment inhibited the levels of cyclooxygenase (COX)-2 mRNA and protein, and the release of prostagladin E2 without alteration of COX-1 expression. Taken together, these findings suggest that resveratrol may be a potential chemotherapeutic agent for the control of human lung carcinorma cells
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KEYWORD
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resveratrol, cell cycle, apoptosis, p21, Bcl-XL, cyclooxygenase
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