Melanoma is a highly aggressive form of
skin cancer with poor survival rate. Aberrant activation of Wnt/β-
catenin has been observed in nearly one-third of human
melanoma cases thereby indicating that targeting Wnt/β-
catenin signaling could be a promising strategy against
melanoma development. In the present study, we determined chemotherapeutic effect of
grape seed proanthocyanidins (GSPs) on the growth of
melanoma cells and validated their protective effects in vivo using a xenograft mouse model, and assessed if β-
catenin is the target of GSP chemotherapeutic effect. Our in vitro data show that treatment of A375 and Hs294t human
melanoma cells with GSPs inhibit the growth of
melanoma cells, which was associated with the reduction in the levels of β-
catenin. Administration of dietary GSPs (0.2 and 0.5%, w/w) in supplementation with AIN76A control diet significantly inhibited the growth of
melanoma tumor xenografts in nude mice. Furthermore, dietary GSPs inhibited the xenograft growth of Mel928 (β-
catenin-activated), while did not inhibit the xenograft growth of Mel1011 (β-
catenin-inactivated) cells. These observations were further verified by
siRNA knockdown of β-
catenin and forced overexpression of β-
catenin in
melanoma cells using a cell culture model.