The Inhibitory Effect of Abietic Acid on Melanoma Cancer Metastasis and Invasiveness In Vitro and In Vivo.
Melanoma cell metastasis is the primary cause of patient death. Thus, various treatment strategies have been developed to prevent metastasis. Abietic acid (AA) is an organic compound commonly found in trees. This study is aimed to investigate the antimetastatic activity of AA in B16F10-xenografted C57BL/6 mice and assess the anticancer activity of AA in combination with Taxol in melanoma cells. AA effectively reduced the formation of lung metastases by approximately 92.8%. AA treatment inhibited migratory potential (p < 0.001), invasion (p < 0.001), and motility (p < 0.001) of highly metastatic B16F10 melanoma cells in vitro. Zymography revealed that AA reduced the proteinase activities of matrix metalloproteinase-2 and urokinase-type plasminogen activator. Molecular analyses showed that AA reduced Akt phosphorylation and activating protein-1 DNA-binding activity by Western blot and electrophoretic mobility shift assay (EMSA), respectively. In summary, AA effectively inhibited B16F10 lung metastasis, and 50[Formula: see text][Formula: see text]M AA did not affect the viability of B16F10 cells. AA improved the efficacy of Taxol and demonstrated strong anticancer activity on melanoma cells. These results suggested that AA could be used as an antimetastatic agent or as an adjuvant for anticancer therapy.