HO-1 up-regulation: A key point in high-risk neuroblastoma resistance to bortezomib

被引：44

作者：

Furfaro, Anna Lisa ^{[1
]}

Piras, Sabrina ^{[1
]}

Passalacqua, Mario ^{[1
]}

Domenicotti, Cinzia ^{[1
]}

Parodi, Alessia ^{[2
]}

Fenoglio, Daniela ^{[2
]}

Pronzato, Maria Adelaide ^{[1
]}

Marinari, Umberto Maria ^{[1
]}

Moretta, Lorenzo ^{[3
]}

Traverso, Nicola ^{[1
]}

Nitti, Mariapaola ^{[1
]}

机构：

[1] Univ Genoa, Dept Expt Med, I-16132 Genoa, Italy

[2] Univ Genoa, Dept Internal Med, Ctr Excellence Biomed Res, I-16132 Genoa, Italy

[3] Giannina Gaslini Inst, I-16147 Genoa, Italy

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2014年 / 1842卷 / 04期

关键词：

Redox signaling; Chemoresistance; Heme oxygenase-1; Neuroblastoma; ACUTE MYELOID-LEUKEMIA; HEME OXYGENASE GENE; PROTEASOME INHIBITION; STRESS-RESPONSE; 26S PROTEASOME; CANCER-CELLS; IN-VIVO; NRF2; ANTIOXIDANT; APOPTOSIS;

D O I：

10.1016/j.bbadis.2013.12.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

High-risk neuroblastoma (NB) is characterized by the development of chemoresistance, and bortezomib (BTZ), a selective inhibitor of proteasome, has been proposed in order to overcome drug resistance. Considering the involvement of the nuclear factor-eiythroid-derived 2-like 2 (Nrf2) and heme oxygenase-1 (HO-1) in the antioxidant and detoxifying ability of cancer cells, in this study we have investigated their role in differently aggressive NB cell lines treated with BTZ, focusing on the modulation of HO-1 to improve sensitivity to therapy. We have shown that MYCN amplified HTLA-230 cells were slightly sensitive to BTZ treatment, due to the activation of Nrf2 that led to an impressive up-regulation of HO-1. BTZ-treated HTLA-230 cells down-regulated p53 and up-regulated p21, favoring cell survival. The inhibition of HO-1 activity obtained by Zinc (II) protoprophyrin IX (ZnPPIX) was able to significantly increase the pro-apoptotic effect of BTZ in a p53- and p21-independent way. However, MYCN non-amplified SH-SY5Y cells showed a greater sensitivity to BTZ in relation to their inability to up-regulate HO-1. Therefore, we have shown that HO-1 inhibition improves the sensitivity of aggressive NB to proteasome inhibition-based therapy, suggesting that HO-1 up-regulation can be used as a marker of chemoresistance in NB. These results open up a new scenario in developing a combined therapy to overcome chemoresistance in high-risk neuroblastoma. (C) 2013 The Authors. Published by Elsevier B.V. All rights reserved.

引用

页码：613 / 622

页数：10

共 56 条

[1]

ALAM J, 1989, J BIOL CHEM, V264, P6371

[2] The role of glutathione in cancer [J].

Balendiran, GK ;

Dabur, R ;

Fraser, D .

CELL BIOCHEMISTRY AND FUNCTION, 2004, 22 (06) :343-352

[3] MYCN oncoprotein targets and their therapeutic potential [J].

Bell, Emma ;

Chen, Lindi ;

Liu, Tao ;

Marshall, Glenn M. ;

Lunec, John ;

Tweddle, Deborah A. .

CANCER LETTERS, 2010, 293 (02) :144-157

[4] Inhibition of heme oxygenase-1 increases responsiveness of pancreatic cancer cells to anticancer treatment [J].

Berberat, PO ;

Dambrauskas, Z ;

Gulbinas, A ;

Giese, T ;

Giese, N ;

Künzli, B ;

Autschbach, F ;

Meuer, S ;

Büchler, MW ;

Friess, H .

CLINICAL CANCER RESEARCH, 2005, 11 (10) :3790-3798

[5] Clinical and pharmacodynamic activity of bortezomib and decitabine in acute myeloid leukemia [J].

Blum, William ;

Schwind, Sebastian ;

Tarighat, Somayeh S. ;

Geyer, Susan ;

Eisfeld, Ann-Kathrin ;

Whitman, Susan ;

Walker, Alison ;

Klisovic, Rebecca ;

Byrd, John C. ;

Santhanam, Ramasamy ;

Wang, Hongyan ;

Curfman, John P. ;

Devine, Steven M. ;

Jacob, Samson ;

Garr, Celia ;

Kefauver, Cheryl ;

Perrotti, Danilo ;

Chan, Kenneth K. ;

Bloomfield, Clara D. ;

Caligiuri, Michael A. ;

Grever, Michael R. ;

Garzon, Ramiro ;

Marcucci, Guido .

BLOOD, 2012, 119 (25) :6025-6031

[6] In vivo degradation of N-myc in neuroblastoma cells is mediated by the 26S proteasome [J].

Bonvini, P ;

Nguyen, P ;

Trepel, J ;

Neckers, LM .

ONCOGENE, 1998, 16 (09) :1131-1139

[7] Effect of bortezomib on human neuroblastoma cell growth, apoptosis, and angiogenesis [J].

Brignole, Chiara ;

Marimpietri, Danilo ;

Pastorino, Fabio ;

Nico, Beatrice ;

Di Paolo, Daniela ;

Cioni, Michela ;

Piccardi, Federica ;

Cilli, Michele ;

Pezzolo, Annalisa ;

Corrias, Maria Valeria ;

Pistoia, Vito ;

Ribatti, Domenico ;

Pagnan, Gabriella ;

Ponzoni, Mirco .

JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2006, 98 (16) :1142-1157

[8] Crosstalk between Nrf2 and the proteasome: Therapeutic potential of Nrf2 inducers in vascular disease and aging [J].

Chapple, Sarah J. ;

Siow, Richard C. M. ;

Mann, Giovanni E. .

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2012, 44 (08) :1315-1320

[9] p53 Is a Direct Transcriptional Target of MYCN in Neuroblastoma [J].

Chen, Lindi ;

Iraci, Nunzio ;

Gherardi, Samuele ;

Gamble, Laura D. ;

Wood, Katrina M. ;

Perini, Giovanni ;

Lunec, John ;

Tweddle, Deborah A. .

CANCER RESEARCH, 2010, 70 (04) :1377-1388

[10] Genome-Wide siRNA Screen for Modulators of Cell Death Induced by Proteasome Inhibitor Bortezomib [J].

Chen, Siquan ;

Blank, Jonathan L. ;

Peters, Theodore ;

Liu, Xiaozhen J. ;

Rappoli, David M. ;

Pickard, Michael D. ;

Menon, Saurabh ;

Yu, Jie ;

Driscoll, Denise L. ;

Lingaraj, Trupti ;

Burkhardt, Anne L. ;

Chen, Wei ;

Garcia, Khristofer ;

Sappal, Darshan S. ;

Gray, Jesse ;

Hales, Paul ;

Leroy, Patrick J. ;

Ringeling, John ;

Rabino, Claudia ;

Spelman, James J. ;

Morgenstern, Jay P. ;

Lightcap, Eric S. .

CANCER RESEARCH, 2010, 70 (11) :4318-4326

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