alpha-carotene and Neoplasm-Metastasis

Several studies have demonstrated that single carotenoid, including lycopene, β-carotene, and α-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 μM) and American (MCA at 1.8 μM) populations using human hepatocarcinoma SK-Hep-1 cells in comparison with single carotenoid, such as lycopene (0.3 or 0.6 μM, respectively), α-carotene (0.1 μM), β-carotene (0.4 μM), lutein (0.4 or 0.5 μM, respectively), and β-cryptoxanthin (0.2 μM). Results reveal that MCA treatment exhibited an additive inhibition on invasion, migration and adhesion at 24 and 48 h of incubation, whereas MCT treatment possessed additive inhibition at 48 h 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 48 h 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.

Topics: beta Carotene; Carcinoma, Hepatocellular; Carotenoids; Cell Adhesion; Cell Line, Tumor; Cell Movement; Cryptoxanthins; Humans; Lutein; Lycopene; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Neoplasm Metastasis; rac1 GTP-Binding Protein; rho-Associated Kinases; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2

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.

Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Carotenoids; Cell Line, Tumor; Cell Movement; Humans; Liver Neoplasms; Matrix Metalloproteinase 2; Mitogen-Activated Protein Kinases; Neoplasm Metastasis; Urokinase-Type Plasminogen Activator