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KMID : 0603820070130020075
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Journal of Experimental & Biomedical Science
2007 Volume.13 No. 2 p.75 ~ p.81
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Sodium Salicylate Induces the Cyclin-dependent Kinase Inhibitor p21 (Waf1/Cip1) through PI3K-related Protein Kinase-dependent p53 Activation in A549 Cells
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Kim Min-Young
Kim Cho-Hee
Hwang Jee-Won
Kim Ji-Hye
Park Hye-Gyeong
Kang Ho-Sung
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Abstract
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Sodium salicylate (NaSal), a chemopreventive drug, has been shown to induce apoptosis and cell circle arrest depending on its concentrations in a variety of cancer cells. In A549 cells, low concentration of NaSal (5sim10 mM) induces cell cycle arrest, whereas it induces apoptosis at higher concentration of 20 mM. In the present study, we examined the molecular mechanism for NaSal-induced cell cycle arrest. NaSal induced expression of p53, p21 (Wafl/Cipl), and p27 (Kipl) that play important roles in cell cycle arrest. p53 induction was mediated by its phosphorylation at Ser-15 that could be prevented by the PI3K-related kinase (ATM, ATR and DNA-PK) inhibitors including wortmannin, caffeine and LY294002. In addition, NaSal-induction of p2l (Wafl/Cipl) was detected in P53 (+/+) wild type A549 cells but not in p53 (-/-) mutant H1299 cells, indicating p53-dependent p21 (Wafl/Cipl) induction. In contrast, p27 (Kipl) that is a negative regulate. of cell cycle with p21 (Wafl/Cipl) was observed both in A549 cells and H1299 cells. Thus, 5 mM NaSal appeared to cause cell cycle arrest through inducing the cyclin-dependent kinase inhibitor p21 (Wafl/Cipl) via PI3K-related protein kinase-dependent p53 activation as well as by up-regulating p27 (Kipl) independently of p53 in A549 cells.
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KEYWORD
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Sodium salicylate, p21, p27, p53, PI3K-related kinase
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