NDLI: Daunorubicin induces cell death via activation of apoptotic signalling pathway and inactivation of survival pathway in muscle-derived stem cells

Content Provider	Springer Nature Link
Author	Stulpinas, Aurimas Imbrasaitė, Aušra Kalvelytė, Audronė Valerija
Copyright Year	2012
Abstract	Daunorubicin (as well as other anthracyclines) is known to be toxic to heart cells and other cells in organism thus limiting its applicability in human cancer therapy. To investigate possible mechanisms of daunorubicin cytotoxicity, we used stem cell lines derived from adult rabbit skeletal muscle. Recently, we have shown that daunorubicin induces apoptotic cell death in our cell model system and distinctly influences the activity of MAP kinases. Here, we demonstrate that two widely accepted antagonistic signalling pathways namely proapoptotic JNK and prosurvival PI3K/AKT participate in apoptosis. Using the Western blot method, we observed the activation of JNK and phosphorylation of its direct target c-Jun along with inactivation of AKT and its direct target GSK in the course of programmed cell death. By means of small-molecule kinase inhibitors and transfection of cells with the genes of the components of these pathways, c-Jun and AKT, we confirm that JNK signalling pathway is proapoptotic, whereas AKT is antiapoptotic in daunorubicin-induced muscle cells. These findings could contribute to new approaches which will result in less toxicity and fewer side effects that are currently associated with the use of daunorubicin in cancer therapies.
Starting Page	103
Ending Page	114
Page Count	12
File Format	PDF
ISSN	07422091
Journal	Cell Biology and Toxicology
Volume Number	28
Issue Number	2
e-ISSN	15736822
Language	English
Publisher	Springer Netherlands
Publisher Date	2012-01-18
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Apoptosis Daunorubicin JNK PI3K/AKT pathway Muscle-derived stem cells Pharmacology/Toxicology Cell Biology Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Health, Toxicology and Mutagenesis Toxicology

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