A Novel Acetylenic Tricyclic bis-(Cyano Enone) Potently Induces Phase 2 Cytoprotective Pathways and Blocks Liver Carcinogenesis Induced by Aflatoxin
| العنوان: | A Novel Acetylenic Tricyclic bis-(Cyano Enone) Potently Induces Phase 2 Cytoprotective Pathways and Blocks Liver Carcinogenesis Induced by Aflatoxin |
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| المؤلفون: | 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 |
| المصدر: | Cancer Research. 68:6727-6733 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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] |
| تدمد: | 1538-7445 0008-5472 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5335bbad1e0982b09b3d8cde1a722ed1Test https://doi.org/10.1158/0008-5472.can-08-1123Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5335bbad1e0982b09b3d8cde1a722ed1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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