Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The covalent modifications of sulfhydryl groups (-SH) may occur through oxidation to mixed disulfides (S-thiolation), S-nitrosylation, as well as persulfide and trisulfide formation. The latter possibilities of -SH group modification connected with compounds containing sulfur called sulfane sulfur are described in this paper. Sulfane sulfur compounds contain a labile, highly reactive sulfur atom at a reduced oxidation state with a valence of 0 or -1, covalently bound to another sulfur atom. These compounds include persulfides, polysulfides, polythionates, thiosulfate, elemental sulfur and disulfides, which enable tautomerization to thiosulfoxides. Sulfane sulfur compounds are formed in the anaerobic cysteine sulfur metabolism with the participation of such enzymes as cystathionase (CST), 3-mercaptopyruvate sulfurtransferase (MpST) and rhodanese (thiosulfate: cyanide sulfurtransferase). Compounds containing sulfane sulfur participate in cell regulation processes through activation or inactivation of some enzymes. Other important roles of sulfane sulfur compounds are their antioxidative properties, significance in the processes of carcinogenesis, participation in the tRNA sulfuration as well as an influence on the activity of immune cells. To recognize completely the biological role of compounds with sulfane sulfur it is necessary to have sensitive methods of quantitative determination, so a review of these methods is presented in this paper. Moreover, biosynthetic pathways and biological properties of these compounds have been discussed.
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PMID:Biosynthesis and biological properties of compounds containing highly reactive, reduced sulfane sulfur. 1178 22

The aim of the present study was to examine the protective effect of cystathionine as a cysteine precursor on doxorubicin toxicity in the liver of Ehrlich ascites tumor (EAT)-bearing mice and in the EAT cells. Both compounds were injected intraperitoneally alone or in combination at the following doses: cystathionine at 10 mg and doxorubicin at 5 mg per kg of body weight. In the liver of EAT-bearing mice, glutathione (GSH), cysteine and sulfane sulfur levels as well as the activities of: glutathione S-transferase, gamma-glutamyl transpeptidase, rhodanese and gamma-cystathionase significantly dropped in comparison with healthy animals. Administration of cystathionine elevated GSH and cysteine levels in the livers of EAT-bearing mice and reduced lipid peroxidation. Furthermore, cystathionine increased gamma-glutamyl transpeptidase activity, thereby activating gamma-glutamyl cycle, responsible for proper glutathione metabolism in the cells. Cystationine did not influence sulfane sulfur level and rhodanese and gamma-cystathionase activity in the livers of EAT-bearing mice. It was next shown that cystathionine administered in combination with doxorubicin protected against the drug toxicity since it elevated thiol level, lowering reactive oxygen species content and suppressing lipid peroxidation. This means that, cystathionine in the liver of EAT-bearing mice can both correct harmful effects of carcinogenesis, and protect the liver from doxorubicin cytotoxicity. In contrast, in EAT cells, cystathionine lowered GSH and cysteine levels and did not alter reactive oxygen species level, lipid peroxidation, and gamma-glutamyl transpeptidase activity. All these data indicate that cystathionine action is selectively beneficial for normal cells because it corrects harmful effects induced by EAT development and protects the organism against doxorubicin cytotoxicity without impairing cytotoxicity of this drug to tumor cells.
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PMID:The selective effect of cystathionine on doxorubicin hepatotoxicity in tumor-bearing mice. 1703 87

NR4A1 (Nur77, TR3) is overexpressed in pancreatic tumors and activation of TR3 by 1,1-bis(3'-indolyl)-1-(p-methoxyphenyl)methane (DIM-C-pPhOCH(3)) inhibits cell and tumor growth and induces apoptosis. Microarray analysis demonstrates that in L3.6pL pancreatic cancer cells DIM-C-pPhOCH(3) induces genes associated with metabolism, homeostasis, signal transduction, transcription, stress, transport, immune responses, growth inhibition and apoptosis. Among the most highly induced growth inhibitory and proapoptotic genes including activating transcription factor 3 (ATF3), p21, cystathionase, dual specificity phosphatase 1 and growth differentiation factor 15, RNA interference studies demonstrated that induction of all but the later gene by DIM-C-pPhOCH(3) were TR3-dependent. We also observed that DIM-C-pPhOCH(3) induced Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and induction of TRAIL was ATF3 dependent. Results of this and previous studies demonstrate that TR3 is unique among nuclear receptors since nuclear TR3 is activated or deactivated by diindolylmethane derivatives to induce different apoptotic and growth inhibitory pathways that inhibit pancreatic cancer cell and tumor growth.
Carcinogenesis 2011 Jun
PMID:Activation of nuclear TR3 (NR4A1) by a diindolylmethane analog induces apoptosis and proapoptotic genes in pancreatic cancer cells and tumors. 2136 29