School of Medicine

Wayne State University School of Medicine

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Q. Ping Dou, Ph.D.
Professor
540.1 Hudson-Webber Cancer
Karmanos Cancer Institute
4100 John R
Detroit, 48201
 
Areas
Cancer Control and Prevention
Biography

The main objective in this laboratory is aimed at discovering molecular targets of chemopreventive agents in pre-clinical studies, followed by validation in targeted cancer prevention clinical trials. Dr. Dou's laboratory is one of the first to report that proteasome inhibitors rapidly induce tumor cell apoptosis, selectively activate the cell death program in oncogene-transformed, but not normal or untransformed cells, and are able to trigger apoptotic death in human cancer cells that are resistant to various anticancer agents. Possible molecular mechanisms involve, at least in part, accumulation of the cyclin-dependent kinase inhibitor p27kip and the apoptosis inducer Bax. In addition, Dr. Dou and his colleagues have shown that proteasome inhibitors suppress human tumor growth in nude mice. Recently, Dr. Dou's laboratory has shown that some tea polyphenols and soy isoflavones potently and specifically inhibit the chymotrypsin-like activity of the proteasome in vitro and in vivo at physiological concentrations. Furthermore, his laboratory has established, for the first time, a computational molecular model that shows how tea polyphenols or soy isoflavones bind and target the proteasome beta5 subunit. This innovative computational model has been validated by comparison of predicted and actual activities of tea polyphenol analogs, either naturally occurring or rationally designed and synthesized. The future targeted prevention trials have been planned to examine whether polyphenols or isoflavones selectively inhibit proteasome activity in human cancer cells and whether such inhibitory activities correlate with clinical effects seen in serum and tissue samples as well as the potential involvement of genetic and environmental risk factor

Education

Ph.D., Rutgers University, 1988

Publications

1. Li, B., and Dou, Q.P. Bax degradation by the ubiquitin/proteasome-dependent pathway: involvement in tumor survival and progression. Proc. Natl. Acad. Sci. USA, 97:3850-3855, 2000.

2. Nam, S., Smith, D.M., and Dou, Q.P. Inhibition of proteasome activity in vitro and in vivo by ester bond-containing tea polyphenols. J. Biol. Chem. 276:13322-13330, 2001.

3. Dou, Q.P., and Goldfarb, R.H., Bortezomib/ PS341 (millennium pharmaceuticals). IDrugs 5:828-834, 2002.

4. Smith, D.M., Wang, Z., Daniel, K.G., Guida, W.C., Chan, T-H, and Dou, Q.P. Mechanistic studies and model development of tea polyphenol proteasome inhibitors: Applications to rational drug design. Proteins: Structure, Function, and Genetics 23:58-70, 2004.

5. Daniel KG, Chen D, Orlu S, Cui QC, Miller FR, and Dou QP. Clioquinol and pyrrolidine dithiocarbamate complex with copper to form proteasome inhibitors and apoptosis inducers in human breast cancer cells. Breast Cancer Res; 7:R897-R908, 2005.

6. Yang HJ, Chen D, Cui QC, Yuan X, and Dou QP. Celastrol, a triterpene extracted from the Chinese Thunder of God Vine, is a potent proteasome inhibitor and suppresses human prostate cancer growth in nude mice. (A figure was selected as the cover of the issue) Cancer Research 66, 4758-4765, May 1, 2006.

7. Kristin R. Landis-Piwowar, Vesna Milacic, Di Chen, Huanjie Yang, Yunfeng Zhao, Tak Hang Chan, Bing Yan, Q. Ping Dou. The Proteasome as a potential target for novel anticancer drugs and chemosensitizers. Drug Resist Updat, 2006; 9: 263-273, 2006.

8. Chen D, Cui QC, Yang HJ, and Dou QP. Disulfiram, A Clinically Used Anti-Alcoholism Drug and Copper-Binding Agent, Induces Apoptotic Cell Death in Breast Cancer Cultures and Xenografts via Inhibition of the Proteasome Activity. Cancer Research 66, 10425-10433, 2006.

Milacic V, Chen D, Ronconi L, Landis-Piwowar KR, Fregona D, and Dou QP. A Novel Anticancer Gold(III) Dithiocarbamate Compound Inhibits the Activity of a Purified 20S Proteasome and 26S Proteasome in Human Breast Cancer Cell Cultures and Xenografts. Cancer Research 66, 10478-10486, 2006.

Chen D, Cui QC, Yang HJ, Barrea RA, Sarkar FH, Sheng S, Yan B, Reddy GPV and Dou QP. Clioquinol, a Therapeutic Agent for Alzheimer’s Disease, Has Proteasome-inhibitory, Androgen Receptor Suppressing, Apoptosis-inducing and Anti-tumor Activities in Human Prostate Cancer Cells and Xenografts. Cancer Res 67: 1636-1644, 2007

Yang HJ, Shi GQ and Dou QP. The Tumor Proteasome Is a Primary Target for the Natural Anticancer Compound Withaferin A Isolated from “Indian Winter Cherry”. Mol Pharmacol. Feb;71(2):426-37, 2007.

Landis-Piwowar KR, Huo CD, Chen D, Cui QC, Minic V, Shi GQ, Chan TH, and Dou QP. A Novel Pro-drug of the Green Tea Polyphenol (-)-Epigallocatechin-3-Gallate as a Potential Anti-Cancer Agent. Cancer Res 67: 4303-4310, 2007.

Landis-Piwowar KR, Wan SB, Wiegand RA, Kuhn DJ, Chan TH, and Dou QP.
Methylation suppresses the proteasome-inhibitory function of green tea
polyphenols.J Cell Physiol. Oct;213(1):252-60, 2007