Ferreira 2017 MITOEAGLE Obergurgl
Event: MitoEAGLE Obergurgl 2017
Doxorubicin (DOX) is a widely used anticancer drug with a limited clinical use because of dose-dependent and cumulative cardiotoxicity. The research on valid strategies to avoid DOX cardiotoxicity involves investigating the mechanisms of toxicity in reliable biological models. DOX-induced cardiotoxicity has been studied in different in vitro models although only a few represent a true cardiac cell model, with the ability to beat in culture.
In this work we used cultured mouse induced pluripotent stem cells (iPSC)-derived cardiomyocytes treated with 0.5 and 1 µM DOX, and measured morphological, functional and biochemical alterations associated with mitochondrial bioenergetics, cellular metabolism, DNA-damage stress responses and apoptosis.
DOX mostly decreased proteins and transcripts associated with mitochondrial bioenergetics and induced p53-dependent caspase activation. Moreover, DOX affected the expression of p53 target transcripts associated with mitochondrial-dependent apoptosis and DNA-damage responses, interestingly in a concentration-independent manner.
In summary, cultured iPSC-derived mouse cardiomyocytes recapitulate markers of DOX cardiotoxicity found in other cardiac-like cell models but also presents some important differences that may be due to the lack of cellular proliferation and/or to the presence of a functional contractile machinery.
• Bioblast editor: Kandolf G
Labels: MiParea: Respiration, Pharmacology;toxicology
Organism: Mouse Tissue;cell: Heart, Stem cells
Event: A1, Oral
Affiliations and support
- CNC, Center Neuroscience Cell Biol, Univ Coimbra, UC Biotech Building, Biocant Park, Cantanhede, Portugal. - firstname.lastname@example.org
- This work was funded by FEDER funds through the Operational Program for Competitiveness Factors—COMPETE and national funds by FCT—Foundation for Science and Technology (PTDC/DTP-FTO/2433/2014 and POCI-01-0145-FEDER-007440). TC-O was supported by a FCT Post-Doctoral fellowship (SFRH/BPD/101169/2014) and LLF (SFRH/BD/52429/2013), ARC (SFRH/BD/103399/2014) and CMD (SFRH/BD/100341/2014) were supported by FCT PhD-fellowships.