However, consistent with previous reported targets,48 withaferin A had significant effects on ER stress and on cellular morphology and inhibited proteasomal activity (data not shown and Supplementary Information) and it was much more toxic to ACHN cells as a single agent than was withanolide E. Critically, siRNA-mediated reduction of cFLIP results in sensitization of renal carcinoma cells to TRAIL-mediated apoptosis,34 demonstrating that the reduction in cFLIP alone is sufficient to sensitize these cells. The gene discussed is CFLAR; the disease is renal carcinoma.