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Cited by 375

The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.

Doxorubicin induces cardiotoxicity through upregulation of death receptors mediated apoptosis in cardiomyocytes

Open access
Zhao, Liqun, Zhang, Baolin·2017·Scientific Reports

Abstract

Doxorubicin is a highly effective anticancer agent but causes cardiotoxicity in many patients. The mechanisms of doxorubicin-induced cardiotoxicity remain incompletely understood. Here we investigated doxorubicin-induced cytotoxicity in human induced pluripotent stem cells-derived cardiomyocytes (iPS-CMs). We found that doxorubicin and related anthracycline agents (e.g., daunorubicin, idarubicin, and epirubicin) significantly upregulated the expression of death receptors (DRs) (TNFR1, Fas, DR4 and DR5) in iPS-derived cardiomyocytes at both protein and mRNA levels. The resulting iPS-CMs cells underwent spontaneous apoptosis which was further enhanced by physiologically relevant death ligands including TNF-related apoptosis inducing ligand (TRAIL). Furthermore, TRAIL potentiated doxorubicin-induced decrease in beating rate and amplitude of iPS-derived cardiomyocytes. These data demonstrate that the induction of death receptors in cardiomyocytes is likely a critical mechanism by which doxorubicin causes cardiotoxicity.

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Crossref · 10.1038/srep44735

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Metadata

Authors
Zhao, L., & Zhang, B.
Venue
Scientific Reports
Published
2017-03-16
Volume
7
Issue
1
Pages
44735-44735
ISSN
2045-2322 (ISSN-L)
OpenAlex
W2596329858
Cited by
375
References
48
FWCI
17.40
Type
journal article
Language
en
Open access
gold

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