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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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General Research Article

Proteomics Analysis of Trastuzumab Toxicity in the H9c2 Cardiomyoblast Cell Line and its Inhibition by Carvedilol

Author(s): Elham Beiranvand, Fatemeh Torkashvand, Seyed N. Ostad, Mehdi Mirzaie, Esmat M. Ardakani, Fatemeh Zandi, Soroush Sardari, Ghasem H. Salekdeh, Mohammad A. Shokrgozar and Behrouz Vaziri*

Volume 21, Issue 13, 2020

Page: [1377 - 1385] Pages: 9

DOI: 10.2174/1389201021666200515135548

Price: $65

Abstract

Objective: Heart dysfunctions are the major complications of trastuzumab in patients with Human Epidermal growth factor Receptor-2 (HER2)-positive breast cancers.

Methods: In this study, the cytotoxicity of trastuzumab on H9c2 cardiomyoblasts was demonstrated, and the proteome changes of cells were investigated by a tandem mass tagging quantitative approach. The Differentially Abundant Proteins (DAPs) were identified and functionally enriched.

Results: We determined that carvedilol, a non-selective beta-blocker, could effectively inhibit trastuzumab toxicity when administrated in a proper dose and at the same time. The proteomics analysis of carvedilol co-treated cardiomyoblasts showed complete or partial reversion in expressional levels of trastuzumab-induced DAPs.

Conclusion: Downregulation of proteins involved in the translation biological process is one of the most important changes induced by trastuzumab and reversed by carvedilol. These findings provide novel insights to develop new strategies for the cardiotoxicity of trastuzumab.

Keywords: Cardiotoxicity, trastuzumab, proteomics, carvedilol, cardiomyoblast, translation.

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[1]
Müller, V.; Clemens, M.; Jassem, J.; Al-Sakaff, N.; Auclair, P.; Nüesch, E.; Holloway, D.; Shing, M.; Bang, Y-J. Long-term trastuzumab (Herceptin®) treatment in a continuation study of patients with HER2-positive breast cancer or HER2-positive gastric cancer. BMC Cancer, 2018, 18(1), 295.
[http://dx.doi.org/10.1186/s12885-018-4183-2] [PMID: 29544445]
[2]
Piotrowski, G.; Gawor, R.; Stasiak, A.; Gawor, Z.; Potemski, P.; Banach, M. Cardiac complications associated with trastuzumab in the setting of adjuvant chemotherapy for breast cancer overexpressing human epidermal growth factor receptor type 2 - a prospective study. Arch. Med. Sci., 2012, 8(2), 227-235.
[http://dx.doi.org/10.5114/aoms.2012.28549] [PMID: 22661994]
[3]
Lemmens, K.; Doggen, K.; De Keulenaer, G.W. Role of neuregulin-1/ErbB signaling in cardiovascular physiology and disease: Implications for therapy of heart failure. Circulation, 2007, 116(8), 954-9460.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.107.690487] [PMID: 17709650]
[4]
Leemasawat, K.; Phrommintikul, A.; Chattipakorn, S.C.; Chattipakorn, N. Mechanisms and potential interventions associated with the cardiotoxicity of ErbB2-targeted drugs: Insights from in vitro, in vivo, and clinical studies in breast cancer patients. Cell. Mol. Life Sci., 2020, 77(8), 1571-1589.
[http://dx.doi.org/10.1007/s00018-019-03340-w] [PMID: 31650186]
[5]
Kabel, A.M.; Elkhoely, A.A. Targeting proinflammatory cytokines, oxidative stress, TGF-β1 and STAT-3 by rosuvastatin and ubiquinone to ameliorate trastuzumab cardiotoxicity. Biomed. Pharmacother., 2017, 93, 17-26.
[http://dx.doi.org/10.1016/j.biopha.2017.06.033] [PMID: 28622591]
[6]
ElZarrad, M.K.; Mukhopadhyay, P.; Mohan, N.; Enkui, H.; Milos, D.; Dianne, S.H.; Yi, S.; Pal, P.; Wen, J.W. Trastuzumab alters the expression of genes essential for cardiac function and induces ultrastructural changes of cardiomyocytes in mice. PLoS One, 2013, 8(11)e79543
[http://dx.doi.org/10.1371/journal.pone.0079543] [PMID: 24255707]
[7]
Gordon, L.I.; Burke, M.A.; Singh, A.T.; Prachand, S.; Lieberman, E.D.; Sun, L.; Naik, T.J.; Prasad, S.V.N.; Ardehali, H. Blockade of the erbB2 receptor induces cardiomyocyte death through mitochondrial and reactive oxygen species-dependent pathways. J. Biol. Chem., 2009, 284(4), 2080-2087.
[http://dx.doi.org/10.1074/jbc.M804570200] [PMID: 19017630]
[8]
Zeglinski, M.; Ludke, A.; Jassal, D.S.; Singal, P.K. Trastuzumab-induced cardiac dysfunction: A ‘dual-hit’. Exp. Clin. Cardiol., 2011, 16(3), 70-74.
[PMID: 22065936]
[9]
Barth, A.S.; Zhang, Y.; Li, T.; Smith, R.R.; Chimenti, I.; Terrovitis, I.; Davis, D.R.; Kizana, E.; Ho, A.S.; O’Rourke, B.; Wolff, A.C.; Gerstenblith, G.; Marbán, E. Functional impairment of human resident cardiac stem cells by the cardiotoxic antineoplastic agent trastuzumab. Stem Cells Transl. Med., 2012, 1(4), 289-297.
[http://dx.doi.org/10.5966/sctm.2011-0016] [PMID: 23197808]
[10]
Gujral, D.M.; Lloyd, G.; Bhattacharyya, S. Effect of prophylactic betablocker or ACE inhibitor on cardiac dysfunction & heart failure during anthracycline chemotherapy ± trastuzumab. Breast, 2018, 37, 64-71.
[http://dx.doi.org/10.1016/j.breast.2017.10.010] [PMID: 29101824]
[11]
Spallarossa, P.; Garibaldi, S.; Altieri, P. et al Carvedilol prevents doxorubicin-induced free radical release and apoptosis in cardiomyocytes in vitro. J. Mol. Cell. Cardiol., 2004, 37(4), 837-846.
[http://dx.doi.org/10.1016/j.yjmcc.2004.05.024] [PMID: 15380674]
[12]
Matsui, H.; Morishima, I.; Numaguchi, Y.; Toki, Y.; Okumura, K.; Hayakawa, T. Protective effects of carvedilol against doxorubicin-induced cardiomyopathy in rats. Life Sci., 1999, 65(12), 1265-1274.
[http://dx.doi.org/10.1016/S0024-3205(99)00362-8] [PMID: 10503942]
[13]
Kalay, N.; Basar, E.; Ozdogru, I. et al Protective effects of carvedilol against anthracycline-induced cardiomyopathy. J. Am. Coll. Cardiol., 2006, 48(11), 2258-2262.
[http://dx.doi.org/10.1016/j.jacc.2006.07.052] [PMID: 17161256]
[14]
Zhang, Y.; Deng, H.; Zhou, H. et al A novel agent attenuates cardiotoxicity and improves antitumor activity of doxorubicin in breast cancer cells. J. Cell. Biochem., 2019, 120(4), 5913-5922.
[http://dx.doi.org/10.1002/jcb.27880] [PMID: 30304553]
[15]
Arbo, M.D.; Altknecht, L.F.; Cattani, S. et alin vitro cardiotoxicity evaluation of graphene oxide. Mutat. Res., 2019, 841, 8-13.
[http://dx.doi.org/10.1016/j.mrgentox.2019.03.004] [PMID: 31138412]
[16]
Enayetallah, A.E.; Puppala, D.; Ziemek, D.; Fischer, J.E.; Kantesaria, S.; Pletcher, M.T. Assessing the translatability of in vivo cardiotoxicity mechanisms to in vitro models using causal reasoning. BMC Pharmacol. Toxicol., 2013, 14, 46.
[http://dx.doi.org/10.1186/2050-6511-14-46] [PMID: 24010585]
[17]
Mosmann, T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods, 1983, 65(1-2), 55-63.
[http://dx.doi.org/10.1016/0022-1759(83)90303-4] [PMID: 6606682]
[18]
Mirzaei, M.; Gupta, V.B.; Chick, J.M. et al Age-related neurodegenerative disease associated pathways identified in retinal and vitreous proteome from human glaucoma eyes. Sci. Rep., 2017, 7(1), 12685.
[http://dx.doi.org/10.1038/s41598-017-12858-7] [PMID: 28978942]
[19]
Deng, L.; Pushpitha, K.; Joseph, C. et al amyloid β induces early changes in the ribosomal machinery, cytoskeletal organization and oxidative phosphorylation in retinal photoreceptor cells. Front. Mol. Neurosci., 2019, 12, 24.
[http://dx.doi.org/10.3389/fnmol.2019.00024] [PMID: 30853886]
[20]
Mirzaei, M.; Pascovici, D.; Wu, J.X.; Chick, J.; Wu, Y.; Cooke, B.; Haynes, P.; Molloy, M.P. TMT one-stop shop: From reliable sample preparation to computational analysis platform. Proteome Bioinformat, 2017, 45-66.
[http://dx.doi.org/10.1007/978-1-4939-6740-7_5]
[21]
Guglin, M.; Krischer, J.; Tamura, R. et al Randomized trial of lisinopril versus carvedilol to prevent trastuzumab cardiotoxicity in patients with breast cancer. J. Am. Coll. Cardiol., 2019, 73(22), 2859-2868.
[http://dx.doi.org/10.1016/j.jacc.2019.03.495] [PMID: 31171092]
[22]
Wisler, J.W.; DeWire, S.M.; Whalen, E.J. et al A unique mechanism of β-blocker action: Carvedilol stimulates β-arrestin signaling. Proc. Natl. Acad. Sci. USA, 2007, 104(42), 16657-16662.
[http://dx.doi.org/10.1073/pnas.0707936104] [PMID: 17925438]
[23]
Noma, T.; Lemaire, A.; Naga, P.S.V. et al Beta-arrestin-mediated beta1-adrenergic receptor transactivation of the EGFR confers cardioprotection. J. Clin. Invest., 2007, 117(9), 2445-2458.
[http://dx.doi.org/10.1172/JCI31901] [PMID: 17786238]
[24]
Kim, I-M.; Tilley, D.G.; Chen, J. et al β-blockers alprenolol and carvedilol stimulate β-arrestin-mediated EGFR transactivation. Proc. Natl. Acad. Sci. USA, 2008, 105(38), 14555-14560.
[http://dx.doi.org/10.1073/pnas.0804745105] [PMID: 18787115]
[25]
Zheng, W.; Shang, X.; Zhang, C.; Gao, X.; Robinson, B.; Liu, J. The effects of carvedilol on cardiac function and the AKT/XIAP signaling pathway in diabetic cardiomyopathy rats. Cardiology, 2017, 136(3), 204-211.
[http://dx.doi.org/10.1159/000450825] [PMID: 27780169]
[26]
Xu, Y.; Benlimame, N.; Su, J.; He, Q.; Alaoui-Jamali, M.A. Regulation of focal adhesion turnover by ErbB signalling in invasive breast cancer cells. Br. J. Cancer, 2009, 100(4), 633-643.
[http://dx.doi.org/10.1038/sj.bjc.6604901] [PMID: 19190626]
[27]
Eldridge, S.; Guo, L.; Mussio, J.; Furniss, M.; Hamre, J. III, Davis, M. Examining the protective role of ErbB2 modulation in human-induced pluripotent stem cell-derived cardiomyocytes. Toxicol. Sci., 2014, 141(2), 547-559.
[http://dx.doi.org/10.1093/toxsci/kfu150] [PMID: 25055963]
[28]
Peng, H.; Gong, P.G.; Li, J.B. et al The important role of the receptor for activated C kinase 1 (RACK1) in nasopharyngeal carcinoma progression. J. Transl. Med., 2016, 14(1), 131.
[http://dx.doi.org/10.1186/s12967-016-0885-x] [PMID: 27170279]
[29]
Gallo, S.; Manfrini, N. Working hard at the nexus between cell signaling and the ribosomal machinery: An insight into the roles of RACK1 in translational regulation Translation, (Austin) 2015, 3(2), e1120382.
[http://dx.doi.org/10.1080/21690731.2015.1120382] [PMID: 26824030]
[30]
Annborn, M.; Dankiewicz, J.; Nielsen, N. et al CT-proAVP (copeptin), MR-proANP and Peroxiredoxin 4 after cardiac arrest: Release profiles and correlation to outcome. Acta Anaesthesiol. Scand., 2014, 58(4), 428-436.
[http://dx.doi.org/10.1111/aas.12282] [PMID: 24617620]
[31]
Kim, E.A.; Na, J.M.; Kim, J.; Choi, S.Y.; Ahn, J.Y.; Cho, S.W. Neuroprotective effect of 3-(naphthalen-2-yl(propoxy)methyl)-azetidine hydrochloride on brain ischaemia/reperfusion injury. J. Neuroimmune Pharmacol., 2017, 12(3), 447-461.
[http://dx.doi.org/10.1007/s11481-017-9733-x] [PMID: 28247179]
[32]
Zlobine, I.; Gopal, K.; Ussher, J.R. Lipotoxicity in obesity and diabetes-related cardiac dysfunction. Biochim. Biophys. Acta, 2016, 1861(10), 1555-1568.
[http://dx.doi.org/10.1016/j.bbalip.2016.02.011] [PMID: 26899197]
[33]
Zamorano-León, J.J.; Modrego, J.; Mateos-Cáceres, P.J. et al A proteomic approach to determine changes in proteins involved in the myocardial metabolism in left ventricles of spontaneously hypertensive rats. Cell. Physiol. Biochem., 2010, 25(2-3), 347-358.
[http://dx.doi.org/10.1159/000276567] [PMID: 20110695]
[34]
Fragasso, G.; Spoladore, R.; Cuko, A.; Palloshi, A. Modulation of fatty acids oxidation in heart failure by selective pharmacological inhibition of 3-ketoacyl coenzyme-A thiolase. Curr. Clin. Pharmacol., 2007, 2(3), 190-196.
[http://dx.doi.org/10.2174/157488407781668776] [PMID: 18690865]
[35]
Podbregar, M.; Voga, G. Effect of selective and nonselective beta-blockers on resting energy production rate and total body substrate utilization in chronic heart failure. J. Card. Fail., 2002, 8(6), 369-378.
[http://dx.doi.org/10.1054/jcaf.2002.130238] [PMID: 12528088]
[36]
Zhuang, L.; Li, C.; Chen, Q. et al Fatty acid-binding protein 3 contributes to ischemic heart injury by regulating cardiac myocyte apoptosis and MAPK pathways. Am. J. Physiol. Heart Circ. Physiol., 2019, 316(5), H971-H984.
[http://dx.doi.org/10.1152/ajpheart.00360.2018] [PMID: 30735072]
[37]
Su, C.C.; Yang, J.Y.; Leu, H.B.; Chen, Y.; Wang, P.H. Mitochondrial Akt-regulated mitochondrial apoptosis signaling in cardiac muscle cells. Am. J. Physiol. Heart Circ. Physiol., 2012, 302(3), H716-H723.
[http://dx.doi.org/10.1152/ajpheart.00455.2011] [PMID: 22081709]
[38]
Krischer, J.; Tamura, R.; Fink, A.; Bello-Matricaria, L.; McCaskill-Stevens, M.; Munster, P.N. Carvedilol suppresses apoptosis and ion channel remodelling of HL-1 cardiac myocytes expressing E334K cMyBPC Drug Res, (Stuttg) 2016, 66(3), 126-129.
[PMID: 26479129]

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