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Literature DB >> 17356134

NPI-0052, a novel proteasome inhibitor, induces caspase-8 and ROS-dependent apoptosis alone and in combination with HDAC inhibitors in leukemia cells.

Claudia P Miller¹, Kechen Ban, Melanie E Dujka, David J McConkey, Mark Munsell, Michael Palladino, Joya Chandra.

Abstract

The proteasome has been successfully targeted for the treatment of multiple myeloma and mantle cell lymphoma; however, in other hematologic malignancies, bortezomib has been less effective as a single agent. Here, we describe effects of NPI-0052, a novel proteasome inhibitor, in leukemia model systems. In cell lines, NPI-0052 inhibits all 3 proteolytic activities associated with the proteasome: chymotrypsin-, trypsin-, and caspase-like. NPI-0052 also induces DNA fragmentation in leukemia lines and in mononuclear cells from a Ph + acute lymphoblastic leukemia (ALL) patient. Caspase-3 activation by NPI-0052 was seen in wild-type Jurkat cells, but was significantly lessened in Fas-associated death domain (FADD)-deficient or caspase-8-deficient counterparts. NPI-0052-induced apoptosis was further probed using caspase-8 inhibitors, which were more protective than caspase-9 inhibitors. N-acetyl cysteine (NAC) also conferred protection against NPI-0052-induced apoptosis, indicating a role for oxidative stress by NPI-0052. In support of the drug's in vitro activities, biweekly treatment with NPI-0052 lessened total white blood cell (WBC) burden over 35 days in leukemic mice. Interestingly, combining NPI-0052 with either MS-275 or valproic acid (VPA) induced greater levels of cell death than the combination of bortezomib with these histone deacetylase inhibitors (HDACi). These effects of NPI-0052, alone and in combination with HDACi, warrant further testing to determine the compound's clinical efficacy in leukemia.

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Year: 2007 PMID： 17356134 PMCID： PMC1896116 DOI： 10.1182/blood-2006-03-013128

Source DB: PubMed Journal: Blood ISSN： 0006-4971 Impact factor: 22.113

49 in total

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Authors: Dieter H Wolf; Wolfgang Hilt
Journal: Biochim Biophys Acta Date: 2004-11-29

3. Proteasome inhibitor MG132 sensitizes HPV-positive human cervical cancer cells to rhTRAIL-induced apoptosis.

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4. Bortezomib inhibits PKR-like endoplasmic reticulum (ER) kinase and induces apoptosis via ER stress in human pancreatic cancer cells.

Authors: Steffan T Nawrocki; Jennifer S Carew; Kenneth Dunner; Lawrence H Boise; Paul J Chiao; Peng Huang; James L Abbruzzese; David J McConkey
Journal: Cancer Res Date: 2005-12-15 Impact factor: 12.701

5. Structure-activity relationship studies of salinosporamide A (NPI-0052), a novel marine derived proteasome inhibitor.

Authors: Venkat R Macherla; Scott S Mitchell; Rama Rao Manam; Katherine A Reed; Ta-Hsiang Chao; Benjamin Nicholson; Gordafaried Deyanat-Yazdi; Bao Mai; Paul R Jensen; William F Fenical; Saskia T C Neuteboom; Kin S Lam; Michael A Palladino; Barbara C M Potts
Journal: J Med Chem Date: 2005-06-02 Impact factor: 7.446

6. Proteasome inhibitors induce apoptosis in glucocorticoid-resistant chronic lymphocytic leukemic lymphocytes.

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7. The proteasome inhibitor bortezomib interacts synergistically with histone deacetylase inhibitors to induce apoptosis in Bcr/Abl+ cells sensitive and resistant to STI571.

Authors: Chunrong Yu; Mohamed Rahmani; Daniel Conrad; Mark Subler; Paul Dent; Steven Grant
Journal: Blood Date: 2003-07-31 Impact factor: 22.113

8. The hierarchical relationship between MAPK signaling and ROS generation in human leukemia cells undergoing apoptosis in response to the proteasome inhibitor Bortezomib.

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Journal: Exp Cell Res Date: 2004-05-01 Impact factor: 3.905

9. Effects of the proteasome inhibitor PS-341 on apoptosis and angiogenesis in orthotopic human pancreatic tumor xenografts.

Authors: Steffan T Nawrocki; Christiane J Bruns; Matthew T Harbison; Richard J Bold; Bridget Sweeney Gotsch; James L Abbruzzese; Peter Elliott; Julian Adams; David J McConkey
Journal: Mol Cancer Ther Date: 2002-12 Impact factor: 6.261

10. Involvement of reactive oxygen species in adaphostin-induced cytotoxicity in human leukemia cells.

Authors: Joya Chandra; Jennifer Hackbarth; Son Le; David Loegering; Nancy Bone; Laura M Bruzek; Ven L Narayanan; Alex A Adjei; Neil E Kay; Ayalew Tefferi; Judith E Karp; Edward A Sausville; Scott H Kaufmann
Journal: Blood Date: 2003-08-14 Impact factor: 22.113

76 in total

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Authors: Tobias A M Gulder; Bradley S Moore
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Review 2. The ubiquitin-proteasome system: opportunities for therapeutic intervention in solid tumors.

Authors: Daniel E Johnson
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3. Distinct TRAIL resistance mechanisms can be overcome by proteasome inhibition but not generally by synergizing agents.

Authors: Christina Menke; Lianghua Bin; Jacqueline Thorburn; Kian Behbakht; Heide L Ford; Andrew Thorburn
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4. Bortezomib interacts synergistically with belinostat in human acute myeloid leukaemia and acute lymphoblastic leukaemia cells in association with perturbations in NF-κB and Bim.

Authors: Yun Dai; Shuang Chen; Li Wang; Xin-Yan Pei; Lora B Kramer; Paul Dent; Steven Grant
Journal: Br J Haematol Date: 2011-03-06 Impact factor: 6.998

5. Treatment-induced oxidative stress and cellular antioxidant capacity determine response to bortezomib in mantle cell lymphoma.

Authors: Marc A Weniger; Edgar G Rizzatti; Patricia Pérez-Galán; Delong Liu; Qiuyan Wang; Peter J Munson; Nalini Raghavachari; Therese White; Megan M Tweito; Kieron Dunleavy; Yihong Ye; Wyndham H Wilson; Adrian Wiestner
Journal: Clin Cancer Res Date: 2011-06-28 Impact factor: 12.531

9. Caspase-8 dependent histone acetylation by a novel proteasome inhibitor, NPI-0052: a mechanism for synergy in leukemia cells.

Authors: Claudia P Miller; Sharmistha Rudra; Michael J Keating; William G Wierda; Michael Palladino; Joya Chandra
Journal: Blood Date: 2009-01-30 Impact factor: 22.113

10. Synergistic apoptosis induction in leukemic cells by the phosphatase inhibitor salubrinal and proteasome inhibitors.

Authors: Hannes C A Drexler
Journal: PLoS One Date: 2009-01-08 Impact factor: 3.240