Multicarotenoids at Physiological Levels Inhibit Metastasis in Human Hepatocarcinoma SK-Hep-1 Cells

Several studies have demonstrated that single carotenoid, including lycopene, beta-carotene, and alpha-carotene, exhibits antimetastatic effects; however, little is known whether multicarotenoids have similar effects. Herein, we investigated the antimetastatic effect of multicarotenoids at physiological serum levels in Taiwanese (MCT at 1.4 mu M) and American (MCA at 1.8 mu M) populations using human hepatocarcinoma SK-Hep-1 cells in comparison with single carotenoid, such as lycopene (0.3 or 0.6 mu M, respectively), alpha-carotene (0.1 mu M), beta-carotene (0.4 mu M), lutein (0.4 or 0.5 mu M, respectively), and beta-cryptoxanthin (0.2 mu M). Results reveal that MCA treatment exhibited an additive inhibition on invasion, migration and adhesion at 24 and 48h of incubation, whereas MCT treatment possessed additive inhibition at 48h of incubation. The antimetastatic action of MCT and MCA involved additive reduction on activities of matrix metalloproteinase (MMP)-2, -9, and protein expression of Rho and Rac 1 but additive promotion on protein expression of tissue inhibitor of MMP (TIMP)-1 and -2. All of these effects were stronger in MCA than in MCT at 24 and 48h of incubation. These results demonstrate that multi-carotenoids effectively inhibit metastasis of human hepatocarcinoma SK-Hep-1 cells. More in vivo studies are needed to confirm these findings.