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

[ Vol. 21 , Issue. 13 ]

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*   Pages 1377 - 1385 ( 9 )

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.

Affiliation:

Protein Chemistry and Proteomics Laboratory, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Protein Chemistry and Proteomics Laboratory, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Department of Molecular Sciences, Macquarie University, Sydney, NSW, Protein Chemistry and Proteomics Laboratory, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Protein Chemistry and Proteomics Laboratory, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Protein Chemistry and Proteomics Laboratory, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Department of Molecular Systems Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Protein Chemistry and Proteomics Laboratory, Biotechnology Research Center, Pasteur Institute of Iran, Tehran



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