Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.22 (cdc2)
 8,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chemical background of the biological activities of vegetables of the Cruciferae family is considered. These vegetables contain alkaloids of the glucobrassicin group that are decomposed by the enzyme myrosinase (thioglucosidase, EC 3.2.3.1) released upon damage to the plant cells. This results in several indole derivatives, with ascorbigen and indole-3-carbinol predominating. In the gastrointestinal tract, these compounds form 5H,11H-indolo[3,2-b]carbazole, natural ligand of the aromatic hydrocarbon receptor (Ah receptor) and a functional analogue of 2,3,7,8-tetrachlorodibenzo-p-dioxin, a dangerous xenobiotic. The indolocarbazole-Ah receptor complex activates the gene of CYP1A1, an isoenzyme of cytochrome P450-dependent monoamine oxidase, which enhances the 2-hydroxylation (inactivation) of estrogens. In its turn, the resulting lowered level of estrogens inhibits the growth of hormone-dependent tumors or prevents their appearance. The mechanism of xenobiotic inactivation, underlying the anticarcinogenic action of food products including vegetables of Cruciferae family and some homogeneous indole compounds, is similar. Some other effects of nutrient indole compounds, e.g., the inhibition of expression of the cyclin-dependent kinase 6 (CDK6) by indole-3-carbinol that leads to the cell cycle arrest in G1 phase, are also considered. Analysis of the biological effects of the Cruciferae diet has helped start clinical studies of indole-3-carbinol as an antitumor and anticarcinogenic remedy for patients with a high risk of tumor diseases.
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PMID:[Indole derivatives in vegetables of the family Cruciferae]. 1080 5

Epidemiological studies recently concluded that consumption of cruciferous vegetables such as broccoli, cabbage, and cauliflower, etc. is inversely related to prostate cancer risk, although the mechanism of prevention and the responsible phytochemicals are unknown. Since clinically significant prostate cancer eventually can grow independent of androgen, the association of the growth and tumorigenesis of such prostate cancer cells with sulforaphane (SFN) which is a predominant isothiocyanate in cruciferous vegetables, investigated. These vegetables contain high concentrations of glucosinolate glucoraphanin, which yield sulforaphane when hydrolyzed by the plant enzyme myrosinase. This study showed that exposure of human androgen-independent DU-145 prostate cancer cells to SFN resulted in the inhibition of growth and tumorigenesis, as revealed by a reduction in cell density, DNA synthesis, and clonogenesis. Analyses of the mechanism revealed that SFN mediated cell cycle arrest by modulating the expression and functions of cell cycle regulators. SFN induced signals that inhibited the activity of cyclin-dependent kinase cdk4 with an up-stream induction of cdk inhibitor p21WAF-1/Cip-1, and reduced cyclin D1. The inhibition of cdk kinase activity could be affected with <1 micro M SFN within 24 h. As a result, phosphorylation of Rb proteins, which activates the transition from G1- to S-phase, was significantly decreased and the cell cycle progression retarded. SFN also down-regulated the expression of bcl-2, a suppressor of apoptosis, and activated caspases to execute apoptosis in the prostate cancer cells. The regulators of cell cycle have thus been revealed as targets of sulforaphane for growth arrest and apoptosis induction. The potential of SFN, as an active dietary factor to inhibit initiation and post-initiation of prostate cancer carcinogenesis is discussed.
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PMID:Targeting cell cycle machinery as a molecular mechanism of sulforaphane in prostate cancer prevention. 1465 56