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KMID : 0606920080160010021
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Biomolecules & Therapeutics
2008 Volume.16 No. 1 p.21 ~ p.27
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Role of Intracellular Calcium in Clotrimazole-Induced Alteration of Cell Cycle Inhibitors, p53 and p27, in HT29 Human Colon Adenocarcinoma Cells
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Pritam Thapa
Kwon Jun-Bum
Kim Jung-Ae
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Abstract
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Clotrimazole (CLT), a potent antifungal drug, is known to inhibit tumor cell proliferation. In the present study, we examined the role of intracellular Ca2+ in CLT-induced cell cycle arrest of colon adenocarcinoma HT29 cells. CLT inhibited growth of HT29 cells in a concentration-dependent manner, which was associated with inhibition of cell cycle progression at the G(1)-S phase transition and an increase in the expression of cell cycle inhibitor proteins p27 and p53. CLT also suppressed the Ca2+ overload by A23187, a calcium ionophore, suggesting its role in modulation of intracellular Ca2+ concentration in HT29 cells. The simultaneous application of CLT and A23187 with addition of CaCl2 (1mM) to the medium significantly reversed CLT-induced p27 and p53 protein level increase and growth suppression. Our results suggest that CLT induces cell cycle arrest of colon adenocarcinoma HT29 cells via induction of p27 and p53, which may, at least in part, be mediated by alteration of intracellular Ca2+ level
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KEYWORD
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Intracellular Ca2+, Cell cycle arrest, Clotrimazole, p27, p53
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