Exosomes derived from embryonic stem cells inhibit doxorubicin and inflammation-induced pyroptosis in muscle cells

Doxorubicin (Dox) is an effective anticancer drug. Unfortunately, it causes cardiac and muscle toxicity due to increased oxidative stress and inflammation; however, it remains unknown whether Dox induces "pyroptosis" - an inflammation-mediated cell death. We investigated whether Dox induces pyroptosis in mouse soleus muscle (Sol 8) cells in vitro and to show the protective effect of embryonic stem cell exosomes (ES-exos) on pyroptosis. Dox and inflammation-induced in vitro model was generated. Pyroptosis was confirmed using immunohistochemistry (with putative markers caspase-1, IL-1β, and pro-inflammatory cytokine IL-18) and Western blotting of caspase-1 and IL-1β. The results show significant increase in the expression of caspase-1, IL-1β, and IL-18 following treatment with Dox, which was inhibited by ES-exos but not mouse embryonic fibroblast exosomes. Moreover, GW4869 compound inhibited functional activity of ES-exos, suggesting these vesicles are key players in the inhibition of pyroptosis. These results suggest that Dox induces inflammatory pyroptosis in Sol 8 cells, which is attenuated by ES-exos in vitro.