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