Malignant melanoma is the most life-threatening
neoplasm of the skin. Despite the increase in incidence,
melanoma is becoming more resistant to current therapeutic agents. The bioactive compound
frugoside has been recently reported to inhibit growth when used in various
cancer cells. However, this effect has not been demonstrated in
melanoma. Here, we found that
frugoside inhibited the rate of reduction of hyperoxidized
peroxiredoxins (Prxs) by downregulating sulfiredoxin (Srx) expression. Furthermore,
frugoside increased the accumulation of sulfinic Prxs and
reactive oxygen species (ROS) and stimulated p-p38 activation, resulting in the mitochondria-mediated death of M14 and A375 human
melanoma cells. The mitochondria-mediated cell death induced by
frugoside was inhibited by the overexpression of Srx and
antioxidants, such as N-acetyl
cysteine and
diphenyleneiodonium. In addition, we observed that
frugoside inhibited
tumor growth without toxicity through a M14 xenograft animal model. Taken together, our findings reveal that
frugoside exhibits a novel antitumor effect based on a ROS-mediated cell death in
melanoma cells, which may have therapeutic implications.