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Mol. Cells 2010; 30(4): 303-310

Published online August 27, 2010

https://doi.org/10.1007/s10059-010-0119-7

© The Korean Society for Molecular and Cellular Biology

(E)-1-(3,4-Dihydroxyphenethyl)-3-Styrylurea Inhibits Proliferation of MCF-7 Cells through G1 Cell Cycle Arrest and Mitochondria-Mediated Apoptosis

Ji-Yeon Yu1,2,3, Ji-Hae Kim1, Tae-Geum Kim2, Beom-Tae Kim2, Yong-Suk Jang2,3, and Jeong-Chae Lee1,2,*

1Institute of Oral Biosciences and Brain Korea 21 Program, Chonbuk National University, Jeonju 561-756, Korea, 2Department of Bioactive Material Sciences and Research Center of Bioactive Materials, Chonbuk National University, Jeonju 561-756, Korea, 3Institute for Molecular Biology and Genetics, Chonbuk National University, Jeonju 561-756, Korea

Correspondence to : *Correspondence: leejc88@jbnu.ac.kr

Received: February 24, 2010; Revised: June 19, 2010; Accepted: June 24, 2010

Abstract

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.

Keywords caspase, G1 cell cycle arrest, MCF-7 breast cancer cells, mitochondria, phenethyl urea derivative

Article

Research Article

Mol. Cells 2010; 30(4): 303-310

Published online October 31, 2010 https://doi.org/10.1007/s10059-010-0119-7

Copyright © The Korean Society for Molecular and Cellular Biology.

(E)-1-(3,4-Dihydroxyphenethyl)-3-Styrylurea Inhibits Proliferation of MCF-7 Cells through G1 Cell Cycle Arrest and Mitochondria-Mediated Apoptosis

Ji-Yeon Yu1,2,3, Ji-Hae Kim1, Tae-Geum Kim2, Beom-Tae Kim2, Yong-Suk Jang2,3, and Jeong-Chae Lee1,2,*

1Institute of Oral Biosciences and Brain Korea 21 Program, Chonbuk National University, Jeonju 561-756, Korea, 2Department of Bioactive Material Sciences and Research Center of Bioactive Materials, Chonbuk National University, Jeonju 561-756, Korea, 3Institute for Molecular Biology and Genetics, Chonbuk National University, Jeonju 561-756, Korea

Correspondence to:*Correspondence: leejc88@jbnu.ac.kr

Received: February 24, 2010; Revised: June 19, 2010; Accepted: June 24, 2010

Abstract

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.

Keywords: caspase, G1 cell cycle arrest, MCF-7 breast cancer cells, mitochondria, phenethyl urea derivative

Mol. Cells
Sep 30, 2023 Vol.46 No.9, pp. 527~572
COVER PICTURE
Chronic obstructive pulmonary disease (COPD) is marked by airspace enlargement (emphysema) and small airway fibrosis, leading to airflow obstruction and eventual respiratory failure. Shown is a microphotograph of hematoxylin and eosin (H&E)-stained histological sections of the enlarged alveoli as an indicator of emphysema. Piao et al. (pp. 558-572) demonstrate that recombinant human hyaluronan and proteoglycan link protein 1 (rhHAPLN1) significantly reduces the extended airspaces of the emphysematous alveoli by increasing the levels of TGF-β receptor I and SIRT1/6, as a previously unrecognized mechanism in human alveolar epithelial cells, and consequently mitigates COPD.

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