| Description: |
alpha-Carotene has anti-metastasis activity, it 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. alpha-Carotene has inhibitory effects on proliferation of the human neuroblastoma cell line GOTO. |
| Targets: |
FAK | MMP(e.g.TIMP) | MAPK |
| In vitro: |
| J Nutr Biochem. 2015 Jun;26(6):607-15. | | 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.[Pubmed: 25736483 ] | This study aimed to investigate the anti-metastatic activity of alpha-Carotene (AC) in Lewis lung carcinoma (LLC) and in combination with taxol in LLC-xenografted C57BL/6 mice.
METHODS AND RESULTS:
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.
CONCLUSIONS:
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. | | J Natl Cancer Inst. 1989 Nov 1;81(21):1649-52. | | Inhibitory effects of alpha-carotene on proliferation of the human neuroblastoma cell line GOTO.[Pubmed: 2795693] |
METHODS AND RESULTS:
alpha-Carotene inhibited the proliferation of the human neuroblastoma cell line GOTO in a dose- and time-dependent manner. In addition, it was about 10 times more inhibitory than beta-carotene. Northern blot analysis indicated that alpha-carotene caused maximum suppression of the level of the N-myc messenger RNA of GOTO cells. This suppression occurred within 18 hours of alpha-carotene treatment, after which the level of the N-myc messenger RNA gradually recovered to the basal level. Analysis by flow cytometry indicated that when GOTO cells were exposed to alpha-carotene, they were arrested in the G0-G1 phase of their cell cycle. However, as the level of the N-myc messenger RNA was recovering, these cells resumed normal cycling.
CONCLUSIONS:
These results indicate that the reduction in the level of the N-myc messenger RNA caused by alpha-carotene is closely linked with G0-G1 arrest. |
|
| In vivo: |
| J Nutr Biochem . 2015 Jun;26(6):607-15. | | 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[Pubmed: 25736483] | | 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.
Keywords: Lewis lung carcinoma; Metastasis; Taxol; α-Carotene; β-Carotene. |
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