Journal
CANCER LETTERS
Volume 237, Issue 1, Pages 130-136Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2005.05.045
Keywords
carnosol; carnosic acid; phenolic diterpenes; cell cycle; cyclins
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Carnosol and carnosic acid, two antioxidant polyphenols present in Rosmarinus officinalis (rosemary), were investigated for their antiproliferative properties toward Caco-2 cells. Twenty hours of treatment with both carnosol and carnosic acid inhibited H-3-thymidine incorporation in a dose-dependent manner, with a 50% inhibitory concentration of 23 mu M and significantly increased the doubling time of Caco-2 cells from 29.5 to 140 and 120 h, respectively. These effects were associated with accumulation of treated cells in the G(2)/M phase of the cell cycle. Carnosol was found to exert its major cell cycle effect after prometaphase, and caused an increase in cyclin B1 protein levels whereas carnosic acid arrested cells prior to prometaphase, and caused a reduction in cyclin A levels. These structurally related phytochemicals, therefore, appear to arrest cells at different phases of the cell cycle possibly through influencing the levels of different cyclin proteins. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
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