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Cancer Therapy
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γ-Secretase inhibitor I induces apoptosis in chronic lymphocytic leukemia cells by proteasome inhibition, endoplasmic reticulum stress increase and notch down-regulation
Article first published online: 17 OCT 2012
DOI: 10.1002/ijc.27863
Copyright © 2012 UICC
Additional Information
How to Cite
Rosati, E., Sabatini, R., De Falco, F., Del Papa, B., Falzetti, F., Di Ianni, M., Cavalli, L., Fettucciari, K., Bartoli, A., Screpanti, I. and Marconi, P. (2013), γ-Secretase inhibitor I induces apoptosis in chronic lymphocytic leukemia cells by proteasome inhibition, endoplasmic reticulum stress increase and notch down-regulation. Int. J. Cancer, 132: 1940–1953. doi: 10.1002/ijc.27863
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Tel.: +39-075-5855830, Fax: +39-075-5855827
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R.S. and F.D.F. contributed equally to this study
Publication History
- Issue published online: 13 FEB 2013
- Article first published online: 17 OCT 2012
- Accepted manuscript online: 24 SEP 2012 02:18AM EST
- Manuscript Accepted: 3 SEP 2012
- Manuscript Revised: 31 AUG 2012
- Manuscript Received: 29 MAR 2012
Funded by
- Progetti di Ricerca di Interesse Nazionale-PRIN (2008). Grant Number: Prot. 2008YSSL7B_003
- Fondazione Cassa di Risparmio di Perugia, Italy (2009). Grant Number: 2009.020.0086
- Associazione Italiana per la Ricerca sul Cancro
References
- 1, , . Chronic lymphocytic leukemia. N Engl J Med 2005; 352: 804–15.
- 2. New agents in chronic lymphocytic leukemia. Curr Hematol Malig Rep 2010; 5: 29–34.
- 3, , , et al. From pathogenesis to treatment of chronic lymphocytic leukaemia. Nat Rev Cancer 2010; 10: 37–50.
- 4, . Targeting multiple kinase pathways: a change in paradigm. Clin Cancer Res 2010; 16: 1973–78.
- 5
- 6, , , et al. Rational targeting of Notch signaling in cancer. Oncogene 2008; 27: 5124–31.
- 7, . Recent insights into the role of Notch signaling in tumorigenesis. Blood 2006; 107: 2223–33.
- 8, . Mechanisms and clinical prospects of Notch inhibitors in the therapy of hematological malignancies. Drug Resist Updat 2008; 11: 210–18.
- 9, , , et al. Constitutively activated Notch signaling is involved in survival and apoptosis resistance of B-CLL cells. Blood 2009; 113: 856–65.
- 10, , , et al. Phase I pharmacokinetic (PK), and pharmacodynamic (PD) trial of the novel oral Notch inhibitor MK-0752 in patients (pts) with advanced breast cancer (BC) and other solid tumors (Meeting Abstract). J Clin Oncol 2006; 24: 10574.
- 11, , , et al. A phase I clinical trial of the Notch inhibitor MK-0752 in patients with T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) and other leukemias (Meeting Abstract). J Clin Oncol 2006; 24: 6585.
- 12, , , et al. Targeting the NF-kappaB signaling pathway in Notch1-induced T-cell leukemia. Nat Med 2007; 13: 70–7.
- 13, , , et al. In vitro validation of gamma-secretase inhibitors alone or in combination with other anti-cancer drugs for the treatment of T-cell acute lymphoblastic leukemia. Haematologica 2008; 93: 533–42.
- 14, , , et al. Targeting both Notch and ErbB-2 signalling pathways is required for prevention of ErbB-2-positive breast tumour recurrence. Br J Cancer 2011; 105: 796–806.
- 15, . A garden of Notch-ly delights. Development 2006; 133: 3277–82.
- 16, , , et al. Inhibition of γ-secretase induces G2/M arrest and triggers apoptosis in breast cancer cells. Br J Cancer 2009; 100: 1879–88.
- 17, , , et al. The cytotoxicity of γ-secretase inhibitor I to breast cancer cells is mediated by proteasome inhibition, not by γ-secretase inhibition. Breast Cancer Res 2009; 11: R57.
- 18, , , et al. z-Leucinyl-leucinyl-norleucinal induces apoptosis of human glioblastoma tumor-initiating cells by proteasome inhibition and mitotic arrest response. Mol Cancer Res 2009; 7: 1822–34.
- 19, , , et al. GSI-I (Z-LLNle-CHO) inhibits γ-secretase and the proteosome to trigger cell death in precursor-B acute lymphoblastic leukemia. Leukemia 2011; 25: 1135–46.
- 20, , , et al. Deregulation of the ubiquitin system and p53 proteolysis modify the apoptotic response in B-CLL lymphocytes. Blood 2000; 96: 269–74.
- 21, , , et al. Phase II study of single-agent bortezomib for the treatment of patients with fludarabine-refractory B-cell chronic lymphocytic leukemia. Cancer 2006; 107: 916–24.
- 22, , . Proteasome-dependent endoplasmic reticulum-associated protein degradation: an unconventional route to a familiar fate. Proc Natl Acad Sci USA 1996; 93: 13797–801.
- 23, . Proteasome inhibitor induces apoptosis through induction of endoplasmic reticulum stress. Cancer Biol Ther 2006; 5: 745–8.
- 24, , , et al. Novel targets for endoplasmic reticulum stress-induced apoptosis in B-CLL. Blood 2010; 116: 2713–23.
- 25, , , et al. Targeting endoplasmic reticulum protein transport: a novel strategy to kill malignant B cells and overcome fludarabine resistance in CLL. Blood 2006; 107: 222–31.
- 26, , , et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) updating the National Cancer Institute-Working Group (NCI-WG) 1996 guidelines. Blood 2008; 111: 5446–56.
- 27, , , et al. A clinical staging system for chronic lymphocytic leukemia: prognostic significance. Cancer 1977; 40: 855–64.
- 28, , , et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 concerted action BMH4-CT98-3936. Leukemia 2003; 17: 2257–317.
- 29, , , et al. ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J Med 2003; 348: 1764–75.
- 30, , , et al. A new genetic lesion in B-CLL: a NOTCH1 PEST domain mutation. Br J Haematol 2009; 146: 689–91.
- 31, , , et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 2004; 306: 269–71.
- 32, , , et al. Diverse marrow stromal cells protect CLL cells from spontaneous and drug-induced apoptosis: development of a reliable and reproducible system to assess stromal cell adhesion-mediated drug resistance. Blood 2009; 114: 4441–50.
- 33, . Mechanisms of proteasome inhibitor action and resistance in cancer. Drug Resist Updat 2008; 11: 164–79.
- 34, . Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ 2004; 11: 381–9.
- 35, , , et al. Caspase cleavage product of BAP31 induces mitochondrial fission through endoplasmic reticulum calcium signals, enhancing cytochrome c release to the cytosol. J Cell Biol 2003; 160: 1115–27.
- 36, , , et al. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 2000; 287: 664–6.
- 37, . Mitochondria and endoplasmic reticulum: the lethal interorganelle cross-talk. J Bioenerg Biomembr 2005; 37: 191–206.
- 38, , , et al. Hierarchical regulation of mitochondrion-dependent apoptosis by BCL-2 subfamilies. Nat Cell Biol 2006; 8: 1348–58.
- 39, . Bodyguards and assassins: Bcl-2 family proteins and apoptosis control in chronic lymphocytic leukaemia. Immunology 2005; 114: 441–9.
- 40, , , et al. Mcl-1 expression has in vitro and in vivo significance in chronic lymphocytic leukemia and is associated with other poor prognostic markers. Blood 2008; 112: 3807–17.
- 41, , , et al. The Akt/Mcl-1 pathway plays a prominent role in mediating antiapoptotic signals downstream of the B-cell receptor in chronic lymphocytic leukemia B cells. Blood 2008; 111: 846–55.
- 42, , , et al. Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation. Genes Dev 2003; 17: 1475–86.
- 43, , , et al. Ets-1 mediates upregulation of Mcl-1 downstream of XBP-1 in human melanoma cells upon ER stress. Oncogene 2011; 30: 3716–26.
- 44, , , et al. Differential Noxa/Mcl-1 balance in peripheral versus lymph node chronic lymphocytic leukemia cells correlates with survival capacity. Blood 2007; 109: 1660–8.
- 45, , . Bcl-2 family regulation by the 20S proteasome inhibitor bortezomib. Oncogene 2008; 27: 1189–97.
- 46, , , et al. Role of NOXA and its ubiquitination in proteasome inhibitor-induced apoptosis in chronic lymphocytic leukemia cells. Haematologica 2010; 95: 1510–18.
- 47, , , et al. Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science 2000; 288: 1053–8.
- 48, . P53 and prognosis: new insights and further complexity. Cell 2005; 120: 7-10.
- 49, , , et al. SEL-10 is an inhibitor of Notch signaling that targets Notch for ubiquitin-mediated protein degradation. Mol Cell Biol 2001; 21: 7403–15.
- 50, , , et al. Notch1 as a potential therapeutic target in cutaneous T-cell lymphoma. Blood 2010; 116: 2504–12.