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Department Affiliation: Pharmacology and Molecular Sciences
Degree: M.D., Yale University School of Medicine
Telephone Number: 410-955-3499
Fax Number: 410-502-6818
E-mail address: email@example.com
School of Medicine Address: 406 Wood Basic Science Building, 725 N. Wolfe St., Baltimore, MD 21205
Molecular mechanisms involved in chemoprotection against cancer.
Chemoprotection against cancer: The susceptibility of animals and their cells to the mutagenic and neoplastic effects of chemical carcinogens and reactive oxygen intermediates depends on the balance between the activities of enzymes involved in the metabolic activation and inactivation (detoxication) of these agents. The activities of these enzymes are regulated by a wide variety of chemical agents and these modulations result in protection against cancer. We have developed animal and cell culture systems for analysis of the molecular signals that regulate detoxication enzymes. With the help of these systems, we have identified and isolated from edible plants (e.g., vegetables) potent enzyme inducers. These minor dietary constituents block chemical carcinogenesis. Biochemical, molecular and cell biological techniques are being used to develop strategies for reducing the risk of developing cancer by identifying phytochemical enzyme inducers in edible plants and evaluating their efficacy in cells, animals, and humans.
- Zhang, Y., Talalay, P., Cho, C.-G., and Posner, G.H. A major inducer of anti-carcinogenic protective enzymes from broccoli: Isolation and elucidation of structure, Proc. Natl. Acad. Sci. USA 89:2399-2403, 1992. Pub Med Reference
- Talalay, P., De Long, M.J., and Prochaska, H.J. Identification of a common chemical signal regulating the induction of enzymes that protect against chemical carcinogenesis, Proc. Natl. Acad. Sci. USA 85:8261-8265, 1988. Pub Med Reference
- Fahey, J.W., Zhang, Y., and Talalay, P. Broccoli sprouts: An exceptionally rich source of inducers of enzymes that protect against chemical carcinogens, Proc. Natl. Acad. Sci. USA 94: 10367-10372, 1997. Pub Med Reference
- Dinkova-Kostova, A.T., Abeygunawardana, C., and Talalay, P. Chemoprotective properties of phenylpropenoids, Bis(benzylidene)cycloalkanones, and related michael reaction Acceptors: Correlation of potencies as phase 2 enzyme inducers and radical scavengers, J. Med. Chem. 41:5278-5296, 1998. Pub Med Reference
- Gao, X, and Talalay, P. Induction of phase 2 genes by sulforaphane protects retinal pigment epithelial cells from photooxidative damage, Proc. Natl. Acad. Sci. USA 101:10446-10451, 2004. Pub Med Reference
- Fahey, J.W., Haristoy, X., Dolan, P.M., Kensler, T.W., Scholtus, I., Stephenson, K.K., Talalay, P., and Lozniewski, A. Sulforaphane inhibits extracellular, intracellular and antibiotic-resistant strains of helicobacter pylori and prevents benzo[a] pyrene-induced stomach tumors. Proc. Natl. Acad. Sci. USA 99:7610-7615, 2002. Pub Med Reference
- Dinkova-Kostova, A.T., Holtzclaw, W.D., Cole, R.N., Itoh, K., Wakabayashi, N., Katoh, Y., Yamamoto, M., and Talalay, P. Direct evidence that sulfhydryl groups of keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants, Proc. Natl. Acad. Sci. USA 99:11908-11913, 2002. Pub Med Reference
- Dinkova-Kostova AT, Cheah J, Samouilov A, Zweier JL, Bozak RE, Hicks RJ, Talalay P. Phenolic Michael reaction acceptors: combined direct and indirect antioxidant defenses against electrophiles and oxidants. Med Chem. 2007 May;3(3):261-8. Pub Med Reference
- Talalay P, Fahey JW, Healy ZR, Wehage SL, Benedict AL, Min C, Dinkova-Kostova AT. Sulforaphane mobilizes cellular defenses that protect skin against damage by UV radiation. Proc Natl Acad Sci U S A. 2007 Oct 30; 104,17500-5. Pub Med Reference
- Liu, H., Dinkova-Kostova, A.T., and Talalay, P. Coordinate Regulation of Enzyme Markers for Inflammation and for Protection against Oxidants and Electrophiles. Proc. Natl. Acad. Sci. USA 105: 15926-15931, 2002. Pub Med Reference