RNA-dependent protein kinase is required for interferon-γ-induced autophagy in MG63 osteosarcoma cells

Osteosarcoma is a bone tumor that mainly affects children and adolescents. Interferons (IFNs) have been shown to exert antitumor effects in osteosarcoma cells, although the molecular mechanisms have not been fully realized. We investigated IFN-gamma actions on osteosarcoma cells. Our results show that IFN-gamma induces the accumulation of autophagosomes in osteosarcoma cells. IFN-gamma treatment leads to the conversion of autophagy marker light chain 3 (LC3)-I to LC3-II in osteosarcoma cells, and this conversion is accompanied by puncta formation. Also, IFN-gamma-mediated induction of autophagosome formation and autophagic flux require RNA-dependent protein kinase (PKR) activity. In addition, our findings show that IFN-gamma-mediated osteosarcoma cell death is not dependent on PKR. Our study suggests that IFN-gamma has differential effects that lead to induction of cell death and autophagy in osteosarcoma cells. Further evaluation of the IFN-gamma-mediated molecular mechanism could lead to improved understanding of and targeted treatment strategies for osteosarcoma.

Automated summary

Interferon-gamma induces autophagosome accumulation in osteosarcoma cells, with conversion of LC3-I to LC3-II and autophagic flux mediated by PKR activity. The cell death induced by IFN-gamma in osteosarcoma cells is independent of PKR. Further understanding of IFN-gamma-mediated molecular mechanisms may lead to improved targeted treatment strategies for osteosarcoma.