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7 June 2001, Volume 20, Number 26, Pages 3428-3436
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Original Paper
Lycopene inhibition of cell cycle progression in breast and endometrial cancer cells is associated with reduction in cyclin D levels and retention of p27Kip1 in the cyclin E-cdk2 complexes
Amit Nahum1, Keren Hirsch1, Michael Danilenko1, Colin KW Watts2, Owen WJ Prall2, Joseph Levy1 and Yoav Sharoni1

1Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev and Soroka Medical Center of Kupat Holim, Beer-Sheva, Israel

2Cancer Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, New South Wales 2010, Australia

Correspondence to: Y Sharoni, Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105, Israel

Abstract

Numerous studies have demonstrated the anticancer activity of the tomato carotenoid, lycopene. However, the molecular mechanism of this action remains unknown. Lycopene inhibition of human breast and endometrial cancer cell growth is associated with inhibition of cell cycle progression at the G1 phase. In this study we determined the lycopene-mediated changes in the cell cycle machinery. Cells synchronized in the G1 phase by serum deprivation were treated with lycopene or vehicle and restimulated with 5% serum. Lycopene treatment decreased serum-induced phosphorylation of the retinoblastoma protein and related pocket proteins. This effect was associated with reduced cyclin-dependent kinase (cdk4 and cdk2) activities with no alterations in CDK protein levels. Lycopene caused a decrease in cyclin D1 and D3 levels whereas cyclin E levels did not change. The CDK inhibitor p21Cip1/Waf1 abundance was reduced while p27Kip1 levels were unaltered in comparison to control cells. Serum stimulation of control cells resulted in reduction in the p27 content in the cyclin E-cdk2 complex and its accumulation in the cyclin D1-cdk4 complex. This change in distribution was largely prevented by lycopene treatment. These results suggest that lycopene inhibits cell cycle progression via reduction of the cyclin D level and retention of p27 in cyclin E-cdk2, thus leading to inhibition of G1 CDK activities. Oncogene (2001) 20, 3428-3436.

Keywords

lycopene; breast cancer; endometrial cancer; cell cycle; cyclin D1; retinoblastoma; p27kip1

Received 3 August 2000; revised 26 February 2001; accepted 7 March 2001
7 June 2001, Volume 20, Number 26, Pages 3428-3436
Table of contents    Previous  Abstract  Next   Full text  PDF