611 Hudson Webber
4100 John R. Street
Detroit, MI 48201
Cancer Targeted Therapy, Chemoprevention, and Ubiquitin-Proteasome System Inhibitors
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, medicinal compounds and organic metal complexes 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 and metal complexes 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.
Jiang L, Wen C, He Q, Sun Y, Wang J, Lan X, Rohondia S, Dou QP, Shi X, Liu J. Pseudolaric acid B induces mitotic arrest and apoptosis in both imatinib-sensitive and -resistant chronic myeloid leukaemia cells. Eur J Pharmacol. 2020;876:173064.
Rohondia SO, Ahmed ZSO, Dou QP. Updated review and perspective on 20S proteasome inhibitors in the treatment of Lung Cancer. Curr Cancer Drug Targets. 2020 Feb 25. [Epub ahead of print]
Yang H, Chen X, Li K, Cheaito H, Yang Q, Wu G, Liu J, Dou QP. Repurposing old drugs as new inhibitors of the ubiquitin-proteasome pathway for cancer treatment. Semin Cancer Biol. 2019;S1044-579X:30411-0.
Jiang L, Sun Y, Wang J, He Q, Chen X, Lan X, Chen J, Dou QP, Shi X, Liu J. Proteasomal cysteine deubiquitinase inhibitor b-AP15 suppresses migration and induces apoptosis in diffuse large B cell lymphoma. J Exp Clin Cancer Res. 2019;38:453.
Xia X, Liao Y, Huang C, Liu Y, He J, Shao Z, Jiang L, Dou QP, Liu J, Huang H. Deubiquitination and stabilization of estrogen receptor α by ubiquitin-specific protease 7 promotes breast tumorigenesis. Cancer Lett. 2019;465:118-28.
Dou QP. Tea in Health and Disease. Nutrients. 2019;11:E929.
Castro I, Ekinci E, Huang X, Cheaito HA, Ahn YH, Olivero-Verbel J, Dou QP. Proteasome-associated cysteine deubiquitinases are molecular targets of environmental optical brightener compounds. J Cell Biochem. 2019;120:14065-75.
Li F, Wang Y, Li D, Chen Y, Dou QP. Are we seeing a resurgence in the use of natural products for new drug discovery? Expert Opin Drug Discov. 2019;14:417-20.
Wu L, Meng F, Dong L, Block CJ, Mitchell AV, Wu J, Jang H, Chen W, Polin L, Yang Q, Dou QP, Wu G. Disulfiram and BKM120 in Combination with Chemotherapy Impede Tumor Progression and Delay Tumor Recurrence in Tumor Initiating Cell-Rich TNBC. Sci Rep. 2019;9:236.
Heyza JR, Arora S, Zhang H, Conner KL, Lei W, Floyd AM, Deshmukh RR, Sarver J, Trabbic CJ, Erhardt P, Chan TH, Dou QP, Patrick SM. Targeting the DNA Repair Endonuclease ERCC1-XPF with Green Tea Polyphenol Epigallocatechin-3-Gallate (EGCG) and Its Prodrug to Enhance Cisplatin Efficacy in Human Cancer Cells. Nutrients. 2018;10:E1644.
Ahmed ZSO, Li X, Li F, Cheaito HA, Patel K, Mosallam ESM, Elbargeesy GA, Dou QP. Computational and Biochemical Studies of Isothiocyanates as Inhibitors of Proteasomal Cysteine Deubiquitinases in Human Cancer Cells. J Cell Biochem. 2018;119:9006-16.
Liao YN, Xia XH, Liu NN, Cai JY, Guo ZQ, Li YL, Jiang LL, Dou QP, Tang DL, Huang HB, and Liu JB. Growth arrest and apoptosis induction in androgen receptor-positive human breast cancer cells by inhibition of USP14-mediated androgen receptor deubiquitination. Oncogene 2018;37:1896-910.
Patel K, Ahmed ZS, Huang X, Yang Q, Ekinci E, Neslund-Dudas CM, Mitra B, Elnady FA, Ahn YH, Yang H, Liu J, Dou QP. Discovering proteasome-associated DUB inhibitors for cancer therapy: Lessons learned from rational design, nature and old drug reposition. Future Med Chem. 2018;10:2087-108.
Li F, Wang Y, Li D, Chen Y, Qiao X, Fardous R, Lewandowski A, Liu JB, Chan TH, Dou QP. Perspectives on the recent developments with green tea polyphenols in drug discovery. Expert Opinion On Drug Discovery 2018;13:643-60.
Viola-Rhenalsa M, Patel KR, Jaimes-Santamaria L, Wu GJ, Liu JB and Dou QP. Recent Advances in Antabuse (Disulfiram): the importance of its metal-binding ability to its anticancer activity. Current Medicinal Chemistry 2018;25:506-24.
Gambini V, Tilio M, Maina EW, Andreani C, Bartolacci C, Wang J, Iezzi M, Ferraro S, Ramadori AT, Simon OC, Pucciarelli S, Wu G, Dou QP, Marchini C, Galassi R, Amici A. In vitro and in vivo studies of gold(I) azolate/phosphane complexes for the treatment of basal like breast cancer. European Journal of Medicinal Chemistry 2018;155:418-27.
Neslund-Dudas CM, McBride RB, Kandegedara A, Rybicki BA, Kryvenko ON, Chitale D, Gupta N, Williamson SR, Rogers CG, Cordon-Cardo C, Rundle AG, Levin AM, Dou QP, Mitra B. Association between cadmium and androgen receptor protein expression differs in prostate tumors of African American and European American men. J Trace Elem Med Biol. 2018;48:233-38.
Soave CL, Guerin T, Liu JB and Dou QP. Targeting the ubiquitin-proteasome system for cancer treatment: discovering novel inhibitors from nature and drug repurposing. Cancer and Metastasis Reviews 2017;36:717-36.
Chen X, Yang Q, Xiao L, Tang D, Dou QP and Liu JB. Metal-based proteasomal deubiquitinase inhibitors as potential anti-cancer agents. Cancer and Metastasis Reviews 2017;36:655-68.
Lucas S (co-first author), Soave C (co-first-author), Nabil G, Ahmed ZSO, Chen G, El-Banna HA, Dou QP (co-corresponding author) and Wang J (co-corresponding author). Pharmacological Inhibitors of NAD biosynthesis as potential anticancer agents. Recent Patents on Anti-Cancer Drug Discovery 2017;12:190-207.
Skrott Z, Mistrik M, Andersen KK, Friis S, Majera D, Gursky J, Ozdian T, Bartkova J, Turi Z, Moudry P, Kraus M, Michalova M, Vaclavkova J, Dzubak P, Vrobel I, Pouckova P, Sedlacek J, Miklovicova A, Kutt A, Li J, Mattova J, Driessen C, Dou QP, Olsen J, Hajduch M, Cvek B, Deshaies RJ, Bartek J. Alcohol-abuse drug disulfiram targets cancer via p97 segregase adapter NPL4. Nature 2017;552:194-9.
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;8:13942-56.
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, Dou QP, Wang XJ, and Liu JB. A novel nickel complex works as a proteasomal deubiquitinase inhibitor for cancer therapy. Oncogene 2016;35:5916-27.
PhD (1988): Rutgers University, New Jersey
CB7210 Fundamentals of Cancer Biology
CB7300 Special Topics - Fundamentals of Cancer Drug Discovery
CB7460 Mechanism of Neoplasia: Alterations to Cellular Signaling