In the present inquiry, we investigated the ability of casticin, a polymethoxyflavone derived from Fructus Viticis, to modulate TRAIL signaling in gastric cancer cells, and our findings suggest that casticin potentiates TRAIL-induced apoptosis in gastric cancer BGC-823, SGC-7901 and MGC-803 cells by (1) inducing DR5 expression and (2) downregulatin of cell survival proteins linked to tumor cell resistance to TRAIL. The gene discussed is TNFSF10; the disease is gastric cancer.