A bis-Benzylidine Piperidone Targeting Proteasome Ubiquitin Receptor RPN13/ADRM1 as a Therapy for Cancer

被引：146

作者：

Anchoori, Ravi K. ^{[1
]}

Karanam, Balasubramanyam ^{[2
]}

Peng, Shiwen ^{[2
]}

Wang, Joshua W. ^{[2
]}

Jiang, Rosie ^{[2
]}

Tanno, Toshihiko ^{[1
]}

Orlowski, Robert Z. ^{[4
]}

Matsui, William ^{[1
]}

Zhao, Ming ^{[1
]}

Rudek, Michelle A. ^{[1
]}

Hung, Chien-fu ^{[2
]}

Chen, Xiang ^{[5
,6
]}

Walters, Kylie J. ^{[5
,6
]}

Roden, Richard B. S. ^{[1
,2
,3
]}

机构：

[1] Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21231 USA

[2] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21231 USA

[3] Johns Hopkins Univ, Dept Gynecol & Obstet, Baltimore, MD 21231 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Div Canc Med, Houston, TX 77030 USA

[5] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA

[6] NCI, Prot Proc Sect, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21702 USA

来源：

CANCER CELL | 2013年 / 24卷 / 06期

基金：

美国国家卫生研究院;

关键词：

OVERCOME BORTEZOMIB RESISTANCE; DEUBIQUITINATING ENZYME; MULTIPLE-MYELOMA; OVARIAN-CANCER; PROTEIN INTERACTOME; 26S PROTEASOME; SYSTEM; SUBUNIT; CELLS; INHIBITOR;

D O I：

10.1016/j.ccr.2013.11.001

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The bis-benzylidine piperidone RA190 covalently binds to cysteine 88 of ubiquitin receptor RPN13 in the 19S regulatory particle and inhibits proteasome function, triggering rapid accumulation of polyubiquitinated proteins. Multiple myeloma (MM) lines, even those resistant to bortezomib, were sensitive to RA190 via endoplasmic reticulum stress-related apoptosis. RA190 stabilized targets of human papillonnavirus (HPV) E6 oncoprotein, and preferentially killed HPV-transformed cells. After oral or intraperitoneal dosing of mice, RA190 distributed to plasma and major organs except the brain and inhibited proteasome function in skin and muscle. RA190 administration profoundly reduced growth of MM and ovarian cancer xenografts, and oral RA190 treatment retarded HPV16(+) syngeneic mouse tumor growth, without affecting spontaneous HPV-specific CD8(+) T cell responses, suggesting its therapeutic potential.

引用

页码：791 / 805

页数：15

共 38 条

[1] Regulators of the Proteasome Pathway, Uch37 and Rpn13, Play Distinct Roles in Mouse Development [J].

Al-Shami, Amin ;

Jhaver, Kanchan G. ;

Vogel, Peter ;

Wilkins, Carrie ;

Humphries, Juliane ;

Davis, John J. ;

Xu, Nianhua ;

Potter, David G. ;

Gerhardt, Brenda ;

Mullinax, Robert ;

Shirley, Cynthia R. ;

Anderson, Stephen J. ;

Oravecz, Tamas .

PLOS ONE, 2010, 5 (10)

[2] Stressing the Ubiquitin-Proteasome System without 20S Proteolytic Inhibition Selectively Kills Cervical Cancer Cells [J].

Anchoori, Ravi K. ;

Khan, Saeed R. ;

Sueblinvong, Thanasak ;

Felthauser, Alicia ;

Iizuka, Yoshie ;

Gavioli, Riccardo ;

Destro, Federica ;

Vogel, Rachel Isaksson ;

Peng, Shiwen ;

Roden, Richard B. S. ;

Bazzaro, Martina .

PLOS ONE, 2011, 6 (08)

[3] Nonproteasomal Targets of the Proteasome Inhibitors Bortezomib and Carfilzomib: a Link to Clinical Adverse Events [J].

Arastu-Kapur, Shirin ;

Anderl, Janet L. ;

Kraus, Marianne ;

Parlati, Francesco ;

Shenk, Kevin D. ;

Lee, Susan J. ;

Muchamuel, Tony ;

Bennett, Mark K. ;

Driessen, Christoph ;

Ball, Andrew J. ;

Kirk, Christopher J. .

CLINICAL CANCER RESEARCH, 2011, 17 (09) :2734-2743

[4] Ubiquitin-proteasome system stress sensitizes ovarian cancer to proteasome inhibitor-induced apoptosis [J].

Bazzaro, M ;

Lee, MK ;

Zoso, A ;

Stirling, WLH ;

Santillan, A ;

Shih, IE ;

Roden, RBS .

CANCER RESEARCH, 2006, 66 (07) :3754-3763

[5] Ubiquitin Proteasome System Stress Underlies Synergistic Killing of Ovarian Cancer Cells by Bortezomib and a Novel HDAC6 Inhibitor [J].

Bazzaro, Martina ;

Lin, Zhenhua ;

Santillan, Antonio ;

Lee, Michael K. ;

Wang, Mei-Cheng ;

Chan, Kwun C. ;

Bristow, Robert E. ;

Mazitschek, Ralph ;

Bradner, James ;

Roden, Richard B. S. .

CLINICAL CANCER RESEARCH, 2008, 14 (22) :7340-7347

[6] α,β-Unsaturated Carbonyl System of Chalcone-Based Derivatives Is Responsible for Broad Inhibition of Proteasomal Activity and Preferential Killing of Human Papilloma Virus (HPV) Positive Cervical Cancer Cells [J].

Bazzaro, Martina ;

Anchoori, Ravi K. ;

Mudiam, Mohana Krishna R. ;

Issaenko, Olga ;

Kumar, Srinivas ;

Karanam, Balasubramanyam ;

Lin, Zhenhua ;

Vogel, Rachel Isaksson ;

Gavioli, Riccardo ;

Destro, Federica ;

Ferretti, Valeria ;

Roden, Richard B. S. ;

Khan, Saeed R. .

JOURNAL OF MEDICINAL CHEMISTRY, 2011, 54 (02) :449-456

[7] Ubiquitin-like protein conjugation and the ubiquitin-proteasome system as drug targets [J].

Bedford, Lynn ;

Lowe, James ;

Dick, Lawrence R. ;

Mayer, R. John ;

Brownell, James E. .

NATURE REVIEWS DRUG DISCOVERY, 2011, 10 (01) :29-46

[8] Administration of HPV DNA vaccine via electroporation elicits the strongest CD8+T cell immune responses compared to intramuscular injection and intradermal gene gun delivery [J].

Best, Simon R. ;

Peng, Shiwen ;

Juang, Chi-Mou ;

Hung, Chien-Fu ;

Hannaman, Drew ;

Saunders, John R. ;

Wu, T. -C. ;

Pai, Sara I. .

VACCINE, 2009, 27 (40) :5450-5459

[9] Crystallography & NMR system:: A new software suite for macromolecular structure determination [J].

Brunger, AT ;

Adams, PD ;

Clore, GM ;

DeLano, WL ;

Gros, P ;

Grosse-Kunstleve, RW ;

Jiang, JS ;

Kuszewski, J ;

Nilges, M ;

Pannu, NS ;

Read, RJ ;

Rice, LM ;

Simonson, T ;

Warren, GL .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1998, 54 :905-921

[10] A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib [J].

Chauhan, D ;

Catley, L ;

Li, GL ;

Podar, K ;

Hideshima, T ;

Velankar, M ;

Mitsiades, C ;

Mitsiades, N ;

Yasui, H ;

Letai, A ;

Ovaa, H ;

Berkers, C ;

Nicholson, B ;

Chao, TH ;

Neuteboom, STC ;

Richardson, P ;

Palladino, MA ;

Anderson, KC .

CANCER CELL, 2005, 8 (05) :407-419

← 1 2 3 4 →