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Open AccessArticle

Rosmarinic Acid as a Candidate in a Phenotypic Profiling Cardio-/Cytotoxicity Cell Model Induced by Doxorubicin

by Qiao Zhang 1,2, Jing Li 1,2, Sha Peng 1,2, Yanling Zhang 1,2,* and Yanjiang Qiao 1,2,*
School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China
Beijing Key Laboratory of Chinese Materia Medica Foundation and New Drug Research and Development, Beijing 100102, China
Authors to whom correspondence should be addressed.
Academic Editor: Thea Magrone
Molecules 2020, 25(4), 836; (registering DOI)
Received: 27 December 2019 / Revised: 8 February 2020 / Accepted: 12 February 2020 / Published: 14 February 2020
Advances in cancer treatment have led to significant improvements in long-term survival in many types of cancer, but heart dysfunction and heart failure, associated with cancer treatment, have also increased. Anthracyclines are the main cause of this type of cardiotoxicity. In this study, we describe a combined experimental and cell morphology analysis approach for the high-throughput measurement and analysis of a cardiomyocyte cell profile, using partial least square linear discriminant analysis (PLS-LDA) as the pattern recognition algorithm. When screening a small-scale natural compound library, rosmarinic acid (RosA), as a candidate drug, showed the same cardioprotective effect as the positive control. We investigated the protective mechanism of RosA on a human cardiomyocyte cell line (AC16) and human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). We showed that RosA pretreatment suppressed doxorubicin (Dox)-induced cell apoptosis and decreased the activity of caspase-9. RosA promotes the expression of Heme oxygenase-1 (HO-1) and reduces the production of reactive oxygen species (Ros), which is induced by Dox. Meanwhile, it can also promote the expression of cardiac-development-related protein, including histone deacetylase 1 (HDAC1), GATA binding protein 4 (GATA4) and troponin I3, cardiac type (CTnI). Collectively, our data support the notion that RosA is a protective agent in hiPSC-CMs and has the potential for therapeutic use in the treatment of cancer therapy-related cardiac dysfunction and heart failure. View Full-Text
Keywords: rosmarinic acid; phenotypic profiling; morphological pattern recognition; hiPSC-CMs rosmarinic acid; phenotypic profiling; morphological pattern recognition; hiPSC-CMs
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MDPI and ACS Style

Zhang, Q.; Li, J.; Peng, S.; Zhang, Y.; Qiao, Y. Rosmarinic Acid as a Candidate in a Phenotypic Profiling Cardio-/Cytotoxicity Cell Model Induced by Doxorubicin. Molecules 2020, 25, 836.

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