MAPK signalling in skeletal muscle-derived stem cells after daunorubicin treatment

Abstract

To shed some light on the cytoxicity of anthracyclines, we developed muscle-derived myogenic stem cell lines (Myo) from different rabbits and examined their susceptibility to various doses of daunorubicin in vitro. We have found that myogenic cells after daunorubicin treatment die by apoptosis, a programmed cell death. Stem cells residing in the tissue, after various damages might be protected and even regenerate the damaged organs. With this in mind, we have tested the involvement of MAPKs – ERK, JNK and p38 – in determination of Myo cell fate. We ascertained the gradual and sustained phosphorylation of JNK and p38 by daunorubicin in Myo cells. To evaluate their role in stem cell survival after daunorubicin treatment, we targeted MAP kinases with specific inhibitors. As a result, the JNK inhibitor SP600125 significantly increased cell viability, showing its proapoptotic mode of action. The other MAP kinase, p38, exhibited an antiapoptotic action, while ERK did not show a significant effect on regulating the fate of cells. Therefore, we propose that JNK inhibitors might be used in combination with the chemotherapeutic drug daunorubicin as a complex treatment increasing stem cell survival and preventing the cardiotoxicity of daunorubicin in cancer patients. Keywords: daunorubicin, MAPK, apoptosis, muscle-derived stem cells