Antimetastatic Effects of α-Carotene and Possible Mechanisms of Action in Human Hepatocarcinoma SK-Hep-1 Cells

In vitro evidence suggests that α-carotene (AC) is an antimetastatic agent against cancer cells, but the mechanistic action is unclear. This study investigated the antimetastatic effect and possible mechanism of AC in comparison with β-carotene (BC) using human hepatocarcinoma SK-Hep-1 cells. Results reveal that treatment with AC (0.5-2.5 μM) for 48 h significantly inhibited invasion, migration, and adhesion of SK-Hep-1 cells in a concentration-dependent manner. These effects of AC were stronger than those of BC at the same concentration (2.5 μM). Mechanistically, AC significantly decreased activities of urokinase plasminogen activator and matrix metalloproteinases (MMP)-2 and -9, but increased protein expression of plasminogen activator inhibitor-1, tissue inhibitor of MMP (TIMP)-1 and -2, and nm23-H1, an antimetastatic protein. AC also attenuated focal adhesion kinase-mediated phosphorylation of mitogen-activated protein kinase family resulting in decreased protein expression of Rho and Rac 1. Overall, these data suggest that AC has potential as an antimetastatic agent.