Ginseng has been used for
cancer prevention. However, little is known about its active components and the molecular mechanisms underlying its effects. Recently, we isolated a unique
lysophosphatidic acid (
LPA) receptor ligand,
gintonin.
Gintonin contains approximately 9.5% LPA, mainly LPA C18:2. Autotaxin (ATX) is responsible for
metastasis by overproducing LPA in
cancers. However, LPA, particularly LPA C18:2, is a strong negative feedback ATX inhibitor. It is unknown whether
gintonin inhibits ATX activity and whether gintonin‑induced ATX inhibition is coupled with antimetastatic activity. In this study, we examined whether
gintonin and LPA C18:2 inhibit ATX activity and metastasis‑related cellular activities in
melanoma cells. We found that
gintonin and LPA C18:2 inhibited the purified and secreted ATX activity from
melanoma cells in a concentration‑dependent manner.
Gintonin also inhibited cell migration with a minimal inhibition of cell growth. The
oral administration of
gintonin or LPA C18:2 inhibited lung
metastasis induced by tail‑vein inoculations of
melanoma cells. Moreover, the
oral administration of
gintonin significantly suppressed the
tumor growth induced by subcutaneous grafts of
melanoma cells. A histological analysis showed that the
oral administration of
gintonin reduced
tumor necrosis, the pleomorphism of
tumor cells,
tumor cell mitosis and angiogenesis. The present study demonstrates that the gintonin‑induced inhibition of ATX activity may be the molecular basis of ginseng‑induced antimetastatic and antitumor activities.