Lycopene inhibits cell migration and invasion and upregulates Nm23-H1 in a highly invasive hepatocarcinoma, SK-Hep-1 cells.
The carotenoid lycopene has been associated with decreased risks of several types of cancer, such as prostate cancer and hepatoma. Tumor metastasis is the most important cause of cancer death. Although lycopene was shown to inhibit metastasis, the mechanism underlying this action is not well understood. Here, we tested the possibility that lycopene may inhibit cancer cell metastasis by upregulating the expression of nm23-H1, a metastasis suppressor gene, in SK-Hep-1 cells, a highly invasive hepatoma cell line, and we determined migration and invasion activities and the expression of nm23-H1 protein and mRNA. We showed that lycopene inhibited SK-Hep-1 migration and invasion in a bell-shaped manner, with the highest effect at 5 micromol/L (91 and 63% inhibition for migration and invasion, respectively; P < 0.05). At the same test level (10 micromol/L), lycopene was much more effective than beta-carotene in reducing cell invasion (by approximately 870%). In contrast to the effects on migration and invasion, lycopene enhanced nm23-H1 expression at both the protein and mRNA levels; the effects were also bell shaped, and at 5 micromol/L, lycopene enhanced nm23-H1 protein and mRNA expressions by 220 +/- 33 and 153 +/- 22% (P < 0.01), respectively. These bell-shaped effects of lycopene may be related to autoxidation of lycopene at elevated concentrations (> or =10 micromol/L). Significant correlations existed between nm23-H1 protein expression and migration (r2= 0.78, P < 0.001) and between nm23-H1 protein expression and invasion (r2= 0.84, P < 0.001) in lycopene-treated SK-Hep-1 cells. We conclude that lycopene has significant antimigration and anti-invasion activity, and that this effect is associated with its induction of nm23-H1 expression.
Huang
Chin-Shiu
CS
Department of Food Science and Biotechnology, National Chung-Hsing University, Taichung, Taiwan, Republic of China.
Shih
Ming-Kuei
MK
Chuang
Cheng-Hung
CH
Hu
Miao-Lin
ML
D016588:Anticarcinogenic Agents / Q000378:metabolism / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000503:physiopathology*; D002338:Carotenoids / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004338:Drug Combinations; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D000077276:Lycopene; D054778:NM23 Nucleoside Diphosphate Kinases; D009361:Neoplasm Invasiveness; D009701:Nucleoside-Diphosphate Kinase / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation; D024502:alpha-Tocopherol / Q000494:pharmacology; D019207:beta Carotene / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D004338:Drug Combinations; D054778:NM23 Nucleoside Diphosphate Kinases; D012333:RNA, Messenger; D019207:beta Carotene; D002338:Carotenoids; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D024502:alpha-Tocopherol; D000077276:Lycopene