Q. Ping Dou
Q. Ping Dou, Ph.D.
540.1 Hudson Webber
4100 John R. Road
Detroit, MI 48201
Mentoring: Richard Arkwright ( Senior Student )
Cancer Targeted Therapy, and Chemoprevention
The main objective in this laboratory is to discover molecular targets of natural products in pre-clinical studies, followed by validation in targeted cancer intervention 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. Dr. Dou's laboratory has also shown that some tea polyphenols and medicinal compounds 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 these natural compounds bind and target the proteasome chymotrypsin subunit. This innovative computational model has been validated by comparison of predicted and actual activities of various analogs, either naturally occurring or rationally designed and synthesized. Recently, Dr. Dou and collaborators have reported that certain copper-binding drugs (such as the antialcoholism drug Disulfiram) can convert the pro-angiogenic copper to a specific cancer cell death inducer. Disulfiram also promotes the conversion of carcinogenic cadmium to a proteasome inhibitor with pro-apoptotic activity in human cancer cells. Finally, environmental toxic organotins target the proteasome in human cells and proteasome inhibition by organotins contributes to their cellular toxicity.
Zhao C, Chen X, Yang C, Zang D, Lan X, Liao S, Zhang P, Wu J, Li X, Liu N, Liao Y, Huang H, Shi X, Jiang L, Liu X, Dou QP, Wang X, Liu J. Repurposing an antidandruff agent to treating cancer: zinc pyrithione inhibits tumor growth via targeting proteasome-associated deubiquitinases. Oncotarget. 2017 Jan 10. [Epub ahead of print]
Arkwright R, Pham TM, Zonder JA, Dou QP. The preclinical discovery and development of bortezomib for the treatment of mantle cell lymphoma. Expert Opin Drug Discov. 2017;12:225-35.
Deshmukh RR, Kim S, Elghoul Y, Dou QP. P-Glycoprotein Inhibition Sensitizes Human Breast Cancer Cells to Proteasome Inhibitors. J Cell Biochem. 2016 Nov 4. [Epub ahead of print]
Zhao C, Chen X, Zang D, Lan X, Liao S, Yang C, Zhang P, Wu J, Li X, Liu N, Liao Y, Huang H, Shi X, Jiang L, Liu X, He Z, Dou QP, Wang X, Liu J. A novel nickel complex works as a proteasomal deubiquitinase inhibitor for cancer therapy. Oncogene. 2016;35:5916-27.
Ahmed RS, Liu G, Renzetti A, Farshi P, Yang H, Soave C, Saed G, El-Ghoneimy AA, El-Banna HA, Foldes R, Chan TH, Dou QP. Biological and Mechanistic Characterization of Novel Prodrugs of Green Tea Polyphenol Epigallocatechin Gallate Analogs in Human Leiomyoma Cell Lines. J Cell Biochem. 2016;117:2357-69.
Deshmukh RR, Dou QP. Proteasome inhibitors induce AMPK activation via CaMKKβ in human breast cancer cells. Breast Cancer Res Treat. 2015;153:79-88.
Sun S, Liu J, Zhou N, Zhu W, Dou QP, Zhou K. Isolation of three new annonaceous acetogenins from Graviola fruit (Annona muricata) and their anti-proliferation on human prostate cancer cell PC-3. Bioorg Med Chem Lett. 2016;26:4382-5.
Liu N, Huang H, Dou QP, Liu J. Inhibition of 19S proteasome-associated deubiquitinases by metal-containing compounds. Oncoscience. 2015;2:457-66. Review.
Schmitt SM, Neslund-Dudas C, Shen M, Cui C, Mitra B, Dou QP. Involvement of ALAD-20S Proteasome Complexes in Ubiquitination and Acetylation of Proteasomal α2 Subunits. J Cell Biochem. 2016;117:144-51.
Farshi P, Deshmukh RR, Nwankwo JO, Arkwright RT, Cvek B, Liu J, Dou QP. Deubiquitinases (DUBs) and DUB inhibitors: a patent review. Expert Opin Ther Pat. 2015;25:1191-208. Review.
Arkwright RT, Deshmukh R, Adapa N, Stevens R, Zonder E, Zhang Z, Farshi P, Ahmed RS, El-Banna HA, Chan TH, Dou QP. Lessons from Nature: Sources and Strategies for Developing AMPK Activators for Cancer Chemotherapeutics. Anticancer Agents Med Chem. 2015;15(5):657-71. Review.
Zhang Z, Bi C, Fan Y, Zhang N, Deshmukh R, Yan X, Lv X, Zhang P, Zhang X, Dou QP. L-Ornithine Schiff base-copper and -cadmium complexes as new proteasome inhibitors and apoptosis inducers in human cancer cells. J Biol Inorg Chem. 2015;20:109-21.
Education and Training
PhD (1988): Rutgers University, New Jersey
Cancer Biology Courses Taught:
CB7460 Mechanism of Neoplasia: Alterations to Cellular Signaling