A Novel Acetylenic Tricyclic bis-(Cyano Enone) Potently Induces Phase 2 Cytoprotective Pathways and Blocks Liver Carcinogenesis Induced by Aflatoxin
| Autor: | Albena T. Dinkova-Kostova, Michael B. Sporn, Hidenori Yoshizawa, Gordon W. Gribble, Chitra Sundararajan, Mark M. Yore, John D. Groopman, Melinda S. Yates, Karen J. Baumgartner, Tadashi Honda, Katherine K. Stephenson, Karen T. Liby, Charlotte R. Williams, Bill D. Roebuck, Darlene B. Royce, Patricia A. Egner, Thomas W. Kensler, Renee Risingsong |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Cancer Research Aflatoxin B1 Administration Oral Nitric Oxide Synthase Type II Apoptosis Nitric Oxide medicine.disease_cause Article Nitric oxide DNA Adducts Mice chemistry.chemical_compound NAD(P)H Dehydrogenase (Quinone) medicine Animals Humans Oleanolic Acid Cells Cultured Cell Proliferation chemistry.chemical_classification Leukemia Molecular Structure biology Cell growth Macrophages Liver Neoplasms Imidazoles Cell Differentiation Phenanthrenes KEAP1 Rats Inbred F344 Rats Nitric oxide synthase Cell Transformation Neoplastic Oncology chemistry Biochemistry biology.protein Reactive Oxygen Species Enone Heme Oxygenase-1 Oxidative stress Tricyclic |
| Zdroj: | Cancer Research. 68:6727-6733 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | A novel acetylenic tricyclic bis-(cyano enone), TBE-31, is a lead compound in a series of tricyclic compounds with enone functionalities in rings A and C. Nanomolar concentrations of this potent multifunctional molecule suppress the induction of the inflammatory protein, inducible nitric oxide synthase, activate phase 2 cytoprotective enzymes in vitro and in vivo, block cell proliferation, and induce differentiation and apoptosis of leukemia cells. Oral administration of TBE-31 also significantly reduces formation of aflatoxin-DNA adducts and decreases size and number of aflatoxin-induced preneoplastic hepatic lesions in rats by >90%. Because of the two cyano enones in rings A and C, TBE-31 may directly interact with DTT and protein targets such as Keap1 that contain reactive cysteine residues. The above findings suggest that TBE-31 should also be tested for chemoprevention and chemotherapy in relevant models of cancer and against other chronic, degenerative diseases in which inflammation and oxidative stress contribute to disease pathogenesis. [Cancer Res 2008;68(16):6727–33] |
| Databáze: | OpenAIRE |
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