Caffeic Acid Induces Autophagy in and Inhibits Migration of Melanoma Cells via Upregulation of 5' Adenosine Monophosphate-Activated Protein Kinase

Caffeic acid, an organic compound found in plants, possesses antioxidant, immunomodulatory, anti-inflammatory, and antitumor activities. Melanoma is a tumor of melanocytes which is associated with poor prognosis. Moreover, treatment of malignant melanoma is difficult. Studies have shown that some antioxidants reduce melanoma cell proliferation by inducing autophagy. The aim of this study is to investigate whether caffeic acid inhibits the tumor properties of melanoma cell line and the death-regulation pathway. We treated melanoma B16-F1 cells with caffeic acid and detected cell motility on migration assay and cell death on MTT assay. Caffeic acid treatment induced autophagy in and decreased mobility of B16-F1 cells. Moreover, levels of autophagy regulators phosphorylated-AKT and phosphorylated-AMPK decreased and increased, respectively, in caffeic acid-treated B16-F1 cells. Furthermore, expression of tumor-related protein FASN, which is activated by AKT and inhibited by AMPK, decreased, while expressions of autophagy-related proteins BECN-1 and LC3 increased, in caffeic acid-treated B16-F1 cells. To investigate the role of AMPK in this regulating pathway, we blocked AMPK phosphorylation using compound C. We observed that inhibition of AMPK phosphorylation partially restores caffeic acid-induced suppression of melanoma cell growth and migration, as well as expressions of autophagy-related proteins BECN-1 and LC3. The results of this study indicate that AMPK is a key regulator of caffeic acid-induced autophagy and provide valuable information for the inhibition and chemoprevention of melanoma.