Department Affiliation: Pharmacology and Molecular Sciences
Degree: M.D., Yale University School of Medicine
Rank: Professor
Telephone Number: 410-955-3499
Fax Number: 410-502-6818
E-mail address: ptalalay@jhmi.edu
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.
Representative Publications:
- 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
- Zhang, Y., Kensler, T.W., Cho, C.-G., Posner, G.H., and Talalay, P. Anticarcinogenic activities of sulforaphane and structurally related synthetic norbornyl isothiocyanates, Proc. Natl. Acad. Sci. USA 91:3147-3150, 1994. 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
- Prestera, T. and Talalay, P. Electrophile and antioxidant regulation of enzymes that detoxify carcinogens, Proc. Natl. Acad. Sci. USA 92:8965-8969, 1995. Pub Med Reference
- Zhao, Q., Yang, X.L., Holtzclaw, W.D., and Talalay, P. Unexpected genetic and structural relationships of a long forgotten flavoenzyme to NAD(P)H:Quinone reductase (DT diaphorase), Proc. Natl. Acad. Sci. USA 94:1669-1674, 1997. 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
- Ramos-Gomez, M., Kwak, M.-K., Dolan, P.M., Itoh, K., Yamamoto, M., Talalay, P., and Kensler, T.W. Sensitivity in carcinogenesis is increased in chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient mice, Proc. Natl. Acad. Sci. USA 98:3410-3415, 2001. 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
- Wakabayashi, N., Dinkova-Kostova, A.T., Holtzclaw, W.D., Kang, M.-I., Kobayashi, A., Yamamoto, M., Kensler, T.W., and Talalay, P. Protection against electrophile and oxidant stress by induction of the phase 2 response: Fate of cysteines of the Keap1 sensor modified by inducers, Proc. Natl. Acad. Sci. USA 101:2040-2045, 2004. Pub Med Reference
Other graduate programs in which Dr. Talalay participates:
BCMB Program
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