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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.
J Nutr Biochem. 2015 Jun; 26(6):607-15.JN

Abstract

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.

Authors+Show Affiliations

Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan.Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan.Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan; Department of the Senior Citizen Service Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.Graduate Institute of Veterinary Pathology, National Chung Hsing University, Taichung, Taiwan.Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan; Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan. Electronic address: mlhuhu@nchu.edu.tw.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25736483

Citation

Liu, Yi-Zhen, et al. "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." The Journal of Nutritional Biochemistry, vol. 26, no. 6, 2015, pp. 607-15.
Liu YZ, Yang CM, Chen JY, et al. 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. J Nutr Biochem. 2015;26(6):607-15.
Liu, Y. Z., Yang, C. M., Chen, J. Y., Liao, J. W., & Hu, M. L. (2015). 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. The Journal of Nutritional Biochemistry, 26(6), 607-15. https://doi.org/10.1016/j.jnutbio.2014.12.012
Liu YZ, et al. 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. J Nutr Biochem. 2015;26(6):607-15. PubMed PMID: 25736483.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Liu,Yi-Zhen, AU - Yang,Chih-Min, AU - Chen,Jen-Yin, AU - Liao,Junn-Wang, AU - Hu,Miao-Lin, Y1 - 2015/02/14/ PY - 2014/06/05/received PY - 2014/11/07/revised PY - 2014/12/12/accepted PY - 2015/3/5/entrez PY - 2015/3/5/pubmed PY - 2016/2/26/medline KW - Lewis lung carcinoma KW - Metastasis KW - Taxol KW - α-Carotene KW - β-Carotene SP - 607 EP - 15 JF - The Journal of nutritional biochemistry JO - J Nutr Biochem VL - 26 IS - 6 N2 - 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. SN - 1873-4847 UR - https://www.unboundmedicine.com/medline/citation/25736483/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0955-2863(15)00028-5 DB - PRIME DP - Unbound Medicine ER -