Cardioprotective role of trans retinoic acid in trastuzumab-induced cardiotoxicity through modulation of Erk2 signalling pathway

Research Article

Received February 28, 2018; Accepted July 27, 2018; Published August 22, 2018
http://dx.doi.org/10.18081/2333-5106/015-10/631-643

Jun Fan ¹, Cheng Yang ¹, Dong-Qing Chin ², Alexis Romanos ¹, Eva Wang ¹, Monica M. Vargas ¹, Hao Cheng ¹

Author Affiliations

a Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, United States. b Department of Cardiovascular Surgery, Hospital of Anhui Medical University, People’s Republic of China.

Abstract

Breast cancer is the most frequent cancer in women, and it is increasingly identified in younger women. The involvement of several oncogenic pathways, including ErbB2, ErbB3, and phosphoinositide 3-kinase (PI3K), has led to the transformation of the ErbB2 receptor in most of the aggressive breast cancers. Chemotherapy and radiation therapy have been used to treat these patients. Moreover, chemicals used in these treatments have numerous side effects, and cardiotoxicity is one of the more critical and studied adverse effects. Cardiotoxicity often involves a dyssynchrony of the contractile cycle in the myocardium and especially mitosis, which is an underlying terminal feature. Trans retinoic acid (tRA), known to be a differentiating molecule, has many protective effects such as anti-differentiation and anti-proliferative effects in several cancers. However, the complete influence of tRA on tyrosine kinase signaling in relation to ErbB2 is still unknown. We are therefore interested in its influence on the ErbB family. The objectives of this study are to investigate the possible chemopreventive effect of tRA on the Trastuzumab-induced cardiotoxicity in newborn rats, to analyze the cardioprotective pathways activated by tRA, and to identify anti-differentiating pathway involved in the mechanism directly or indirectly through the induction of trophic factor, desmoplakin, and by modulating signaling molecules associated with differentiation, such as CaM, DcR3, and Erk1 and 2.

Keywords: Trastuzumab; Breast cancer; Cardiac dysfunction; Trans retinoic acid

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