Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/8473
Title: Extended treatment of cancer cells with physiological concentrations of dietary phytochemicals results in altered gene expression, reduced growth and apoptosis
Authors: Moiseeva, Elena P.
Almeida, G. M.
Jones, George D. D.
Manson, M. M.
First Published: Nov-2007
Publisher: American Association for Cancer Research
Citation: Molecular Cancer Therapeutics, 2007, 6(11), pp.3071-9.
Abstract: Dietary phytochemicals exhibit chemopreventive potential in vivo through persistent low-dose exposures, whereas mechanistic in vitro studies with these agents generally use a high-dose single treatment. Because the latter approach is not representative of an in vivo steady state, we investigated antitumor activity of curcumin, 3,3′-diindolylmethane (DIM), epigallocatechin gallate (EGCG), genistein, or indole-3-carbinol (I3C) in breast cancer MDA-MB-231 cells, exposed in long-term culture to low concentrations, achievable in vivo. Curcumin and EGCG increased cell doubling time. Curcumin, EGCG, and I3C inhibited clonogenic growth by 55% to 60% and induced 1.5- to 2-fold higher levels of the basal caspase-3/7 activity. No changes in expression of cell cycle–related proteins or survivin were found; however, I3C reduced epidermal growth factor receptor expression, contributing to apoptosis. Because some phytochemicals are shown to inhibit DNA and histone modification, modulation of expression by the agents in a set of genes (cadherin-11, p21Cip1, urokinase-type plasminogen activator, and interleukin-6) was compared with changes induced by inhibitors of DNA methylation or histone deacetylation. The phytochemicals modified protein and/or RNA expression of these genes, with EGCG eliciting the least and DIM the most changes in gene expression. DIM and curcumin decreased cadherin-11 and increased urokinase-type plasminogen activator levels correlated with increased cell motility. Curcumin, DIM, EGCG, and genistein reduced cell sensitivity to radiation-induced DNA damage without affecting DNA repair. This model has revealed that apoptosis and not arrest is likely to be responsible for growth inhibition. It also implicated new molecular targets and activities of the agents under conditions relevant to human exposure.
DOI Link: 10.1158/1535-7163.MCT-07-0117
ISSN: 1535-7163
eISSN: 1538-8514
Links: http://hdl.handle.net/2381/8473
http://mct.aacrjournals.org/content/6/11/3071
Type: Article
Description: This is the authors' final draft of the article published as Molecular Cancer Therapeutics, 2007, 6(11), pp.3071-9. The original published version is available at http://mct.aacrjournals.org/content/6/11.toc DOI: 10.1158/1535-7163.MCT-07-0117
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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