Frugoside가 인간 흑색종 세포의 세포사멸에 미치는 영향

Abstract

Malignant melanoma is the most life-threatening neoplasm of the skin, accounting for most of the skin cancer deaths. Its incidence is increasing worldwide and it is becoming resistant to current therapeutic agents. The bioactive compound frugoside, a new cardenolide glycoside from the leaves of Calotropis procera W.T. Aiton (family Asclepiadaceae), was recently reported to inhibit the growth of various human cancer cell lines in vitro. However, its modes of action on melanoma cancer have not been clearly defined. Here, I have shown that frugoside selectively inhibited the viability of human melanoma cancer M14 and A375 cells in a concentration- and time-dependent manner. Frugoside could significantly increase the generation of reactive oxygen species (ROS), which triggered the mitochondrial/caspase apoptotic pathway in M14 and A375 cells. The reducing of ROS generation with antioxidant N-acetyl-L-cystein and dipenyleneiodonium (DPI) conferred significant protection against frugoside-induced ROS generation, disruption of apoptotic mechanisms including loss of mitochondrial membrane potential, release of cytochrome-c, and activation of the caspase-cascade. Finally, frugoside exhibited a potential antitumor effect in M14 melanoma cancer xenografts without apparent toxicity. Taken together, the present study indicates that frugoside can induce melanoma cancer cell apoptosis and therefore represents therapeutic potential for cancer treatment.