Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Extended treatment with physiologic concentrations of dietary phytochemicals results in altered gene expression, reduced growth, and apoptosis of cancer cells. 1802 90

Indole compounds, obtained from cruciferous vegetables, have been investigated for their putative anti-cancer properties. Studies with indole-3-carbinol (I3C) and its dimeric product, 3, 3' diindolylmethane (DIM), have indicated efficacy of these compounds against a number of human cancers. Available as well as emerging data suggests that these compounds act on a number of cellular signaling pathways leading to their observed biological effects. Such pleiotropic effects of these compounds are also considered crucial for their chemosensitization activity wherein they help reduce the toxicity and resistance against conventional chemotherapeutic drugs. These observations have major clinical implications especially in chemotherapy. Through this review, we have attempted to update current understanding on the state of anti-cancer research involving indole compounds. We have also summarized the available literature on modulatory effects of indoles on molecular targets such as survivin, uPA/uPAR and signaling pathways such as the NF-kappaB pathway, which are important for the apoptosis-inducing and chemosensitizing properties of these compounds.
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PMID:Anticancer properties of indole compounds: mechanism of apoptosis induction and role in chemotherapy. 2029 56

Cancer affects the lives of millions of people. Several signaling pathways have been proposed as therapeutic targets for cancer therapy, and many more continue to be validated. With the identification and validation of therapeutic targets comes the question of designing novel strategies to effectively counter such targets. Natural compounds from dietary sources form the basis of many ancient medicinal systems. They are pleiotropic i.e. they act on multiple targets, and, therefore, are often the first agents to be tested against a novel therapeutic target. This review article summarizes the knowledge so far on some actively pursued targets - Notch, CXCR4, Wnt and sonic hedgehog (shh) pathways, the process of epithelial-mesenchymal transition (EMT) as well as molecular markers such as uPA-uPAR, survivin, FoxM1, and the microRNAs. We have performed an extensive survey of literature to list modulation of these targets by natural agents such as curcumin, indole-3-carbinol (I3C), 3,3'-diindolylmethane (DIM), resveratrol, epigallocatechin-3-gallate (EGCG), genistein etc. We believe that this review will stimulate further research for elucidating and appreciating the value of these wonderful gifts from nature.
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PMID:Novel targets for detection of cancer and their modulation by chemopreventive natural compounds. 2220 83