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KMID : 0578320100300040303
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Molecules and Cells
2010 Volume.30 No. 4 p.303 ~ p.310
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(E)-1-(3,4-Dihydroxyphenethyl)-3-Styrylurea Inhibits Proliferation of MCF-7 Cells through G1 Cell Cycle Arrest and Mitochondria-Mediated Apoptosis
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Yu Ji-Yeon
Kim Ji-Hae
Kim Tae-Geum
Kim Beom-Tae
Jang Yong-Suk
Lee Jeong-Chae
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Abstract
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Growing interest in the beneficial effects of antioxidants has inspired the synthesis of new phenolic acid phenethyl ureas (PAPUs) with enhanced antioxidant potential. We have previously shown the capacity of one PAPU compound, (E)-1-(3,4-dihydroxyphenethyl)-3-styrylurea (PAPU1), to induce caspase-dependent apoptosis in mela-noma cells. In the present study, we examined the anti-proliferative effects of PAPU compounds on MCF-7 human breast cancer cells and determined the molecular mechanisms involved. Treatment with PAPU compounds inhibited predominantly proliferation in these cells, where the PAPU1 was the most efficient form. Flow cytometric analysis showed that PAPU1 blocked cell cycle progression in the G0/G1 phase, and reduced the proportion of cells in G2/M phase. This was related to the inhibition of cell cycle regulatory factors, including cyclin D/E and cyclin-dependent kinase (CDK) 2/4, through induction of p21Cip1. PAPU1 also induced the mitochondrial-mediated and caspase-depen-dent apoptosis in MCF-7 cells. This was evidenced by cellular changes in the levels of Bcl-2 and Bax, loss of the mitochondrial membrane potential, release of cyto-chrome c into the cytosol, and caspase-9 activation. Col-lectively, our results suggest that G1 cell cycle regulatory proteins and mitochondrial pathways are the crucial targets of PAPU1 in the chemoprevention of breast cancer cells.
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KEYWORD
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caspase, G1 cell cycle arrest, MCF-7 breast cancer cells, mitochondria, phenethyl urea derivative
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