Alpha-carotene inhibits metastasis in Lewis lung carcinoma in vitro, and suppresses lung metastasis and tumor growth in combination with taxol in tumor xenografted C57BL/6 mice

• DOI: 10.1016/j.jnutbio.2014.12.012
• Publication Date: 2015-02-14T07:01:13Z
• Authors: Yi-Zhen Liu; Chih-Min Yang; Jen-Yin Chen; Junn-Wang Liao; Miao-Lin Hu
• Keywords: Male; Lung Neoplasms; Paclitaxel; Taxol; β-Carotene; Metastasis; Carcinoma, Lewis Lung; Mice; 03 medical and health sciences; 0302 clinical medicine; Plasminogen Activator Inhibitor 1; Animals; Tissue Inhibitor of Metalloproteinase-2; Tissue Inhibitor of Metalloproteinase-1; α-Carotene; Antineoplastic Agents, Phytogenic; Carotenoids; Urokinase-Type Plasminogen Activator; Xenograft Model Antitumor Assays; 3. Good health; Mice, Inbred C57BL; Matrix Metalloproteinase 9; Focal Adhesion Kinase 1; Lewis lung carcinoma; Matrix Metalloproteinase 2

This study aimed to investigate the anti-metastatic activity of α-carotene (AC) in Lewis lung carcinoma (LLC) and in combination with taxol in LLC-xenografted C57BL/6 mice. Cell culture studies reveal that AC significantly inhibited invasion, migration and activities of matrix metalloproteinase (MMP)-2, -9 and urokinase plasminogen activator but increased protein expression of tissue inhibitor of MMP (TIMP)-1, -2 and plasminogen activator inhibitor (PAI)-1. These effects of AC are similar to those of β-carotene at the same concentration (2.5 μM). AC (2.5 μM) also significantly inhibited integrin β1-mediated phosphorylation of focal adhesion kinase (FAK) which then decreased the phosphorylation of MAPK family. Findings from the animal model reveal that AC treatment (5m g/kg) alone significantly decreased lung metastasis without affecting primary tumor growth, whereas taxol treatment (6 mg/kg) alone exhibited significant inhibition on both actions, as compared to tumor control group. AC treatment alone significantly decreased protein expression of integrin β1 but increased protein expression of TIMP-1 and PAI-1 without affecting protein expression of TIMP-2 and phosphorylation of FAK in lung tissues, whereas taxol treatment alone significantly increased protein expression of TIMP-1, PAI-1 and TIMP-2 but decreased protein expression of integrin β1 and phosphorylation of FAK. The combined treatment produced stronger actions on lung metastasis and lung tissues protein expression of TIMP-1, TIMP-2 and PAI-1. Overall, we demonstrate that AC effectively inhibits LLC metastasis and suppresses lung metastasis in combination with taxol in LLC-bearing mice, suggesting that AC could be used as an anti-metastatic agent or as an adjuvant for anti-cancer drugs.