Ornithine decarboxylase cancer cell inhibition

Resveratrol exerts antitumor effects partly by arresting the growth of various cancer cells in culture [Kundu and Surh, 2004]. The inhibition of ornithine decarboxylase (ODC), a biochemical hallmark of tumor promotion, has been shown to account for the antiproliferative and antitumor effects of resveratrol [Schneider et al., 2000 Ulrich et al., 2007]. Aberrant changes in cell-cycle machinery are considered as the biochemical basis of abnormal proliferation of transformed cells. Major cell-cycle regulatory proteins include various cyclins, cyclin-dependent kinases (Cdk), Cdk inhibitors, and check point kinases (Chkl... 

White EL, Ross LJ, Schmid SM, Kelloff GJ, Steele VE, Hill DL. 1998a. Screening of potential cancer-preventing chemicals for inhibition of induction of ornithine decarboxylase in epithelial cells from rat trachea. Oncol Rep 5 717-722. 

We first assessed the effects of apigenin on ornithine decarboxylase (ODC) activity, a marker of cell proliferation, in cultured human colon cancer cells (Caco-2). ODC activity was measured by assessing the release of CO2 from 1-C -ornithine. Apigenin treatment for 15 to 39 h at 10 or 30 pM inhibited the ODC in the cultured colonic Caco-2 cells by 26 5 and 57 12%, respectively, when compared with the vehicle (p < 0.01). Studies in CF-1 mice determined dietary apigenin effects on ODC and ACF, precursors of colon cancer. These studies in mice demonstrated that dietary apigenin fed at 0.1 % for 1 week reduced the colonic basal ODC activity by 42 23% in comparison with control diet (p < 0.01). Because ODC was inhibited by only 1 week of dietary apigenin at... 

Wu,F., Grossenbacher, D., and Gehring, H. (2007) New transition state-based inhibitor for human ornithine decarboxylase inhibits growth of tumor cells. Mol. Cancer Ther. 6, 1831-1839. 

NO has a cytostatic effect by inhibiting ATP synthesis [99] via Kreb s cycle (aconitase inhibition, [100]), glycolysis (GADPH inhibition) and mitochondrial respiration (NAD ubiquinone oxydoreductase and succinate ubiquinone oxydoreductase inhibitions, [101]). Another pathway is the ornithine decarboxylase inhibition. This enzyme is implicated in polyamine production necessary to cell proliferation and its activity is inhibited by NO in human colon cancer cells HT-29 and Caco-2 [102]. Furthermore NO directly inactivates ribonucleotide reductase [103] of TA3 cancer cells (murine breast cancer cells) [104]. This enzyme controlling DNA synthesis catalyses desoxyribonucleotides synthesis, and its inhibition blocks cells in S phase. This inhibition is rapid and reversible in K562 and TA3 cells [105]. 

In an effort to determine the cancer chemopreventive activity of tea compounds, we conducted several in vitro mechanistic assays and in vitro cell-transformation assays to screen for efficacy of these compounds. The mechanistic assays measure (a) inhibition of DNA adduct formation, (b) inhibition of free-radical formation, and (c) enhancement of glutathione (GSH), glutathione-S-transferase (GST), ornithine decarboxylase (ODC), and NAD(P)H quinone reductase (QR) activity. No extracts were positive in all six assays, but several were positive in four to five assays. 

Caffeic Acid Phenethyl Ester (CAPE). CAPE, a phenolic compound with antioxidant properties, is an active ingredient derived from honeybee propolis (52). CAPE has antiviral, anti-inflammatory and antiproliferative properties. The compound differentially suppresses the growth of numerous human cancer cells and also inhibits tumor promoter-mediated processes in transformed cells (53,54). In transformed cells, CAPE induces apoptosis and inhibits the expression of the malignant phenotype (55,56). In addition, CAPE treatment attenuates the formation of azoxymethane-induced aberrant crypts and the activities of ornithine decarboxylase (ODC), tyrosin protein kinase, and lipoxygenase activity (57). Although the molecular basis for these multiple chemopreventive effects of CAPE is not clear, recent studies have demonstrated that CAPE is a potent and specific inhibitor of the transcription factor NF-kB (58). CAPE inhibited the activity and expression of COX-2 in the carrageenan air pouch model of inflammation as well as in TPA-treated human oral epithelial cells (59). CAPE was able to reduce neointimal formation by inhibiting NF-kB activation in a model of endothelial injury of rat carotid artery (60). 

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