Fungal secondary metabolite rasfonin enhances sunitinib-induced autophagy and apoptosis in renal carcinoma cells

Abstract:

[Objective] We studied the regulatory role of rasfonin in mediating sunitinib induced autophagy and apoptosis.[Methods] We used both methanethiosulfonate assay and colony growth assay to detect the cell viability and proliferation. In addition, we used electronic and fluorescence microscopy to examine the formation of autophagosome, as well as carried out immunofluorescence or immunoblotting to determine autophagy and apoptosis.[Results] Both rasfonin and sunitinib could induce autophagy and caspase-dependent apoptosis in renal carcinoma cells. Notably, low dose of rasfonin enhanced sunitinib-dependent autophagy and apoptosis, meanwhile sunitinib and rasfonin synergistically inhibited cell viability. In addition, both sunitinib and rasfonin inhibited the phosphorylation of mammal target of rapamycin and increased the activity of extracellular regulated protein kinases.[Conclusion] Rasfonin promotes sunitinib-induced autophagy and caspase dependent apoptosis, and strengthens the cytotoxic effect of sunitinib in renal carcinoma cells.