Lycopene inhibits experimental metastasis of human hepatoma SK-Hep-1 cells in athymic nude mice.
Lycopene has been shown to inhibit tumor metastasis in vitro, but it is unclear whether lycopene is antimetastatic in vivo. Here, nude mice were orally supplemented 2 times per week for 12 wk with a low or high dose of lycopene [1 or 20 mg/kg body weight (BW)] or with beta-carotene (20 mg/kg BW). Two weeks after the beginning of supplementation, mice were injected once with human hepatoma SK-Hep-1 cells via the tail vein. Plasma levels of matrix metalloproteinase (MMP)-2 and vascular endothelial growth factor (VEGF) increased gradually in tumor-injected mice (tumor controls) following tumor injection but were markedly lowered by lycopene or beta-carotene supplementation. Ten weeks after tumor injection, mice were killed and tumor metastasis was found to be confined to the lungs. Compared with the tumor controls, high-lycopene supplementation lowered the mean number of tumors from 14 +/- 8 to 3 +/- 5 (P < 0.05) and decreased tumor cross-sectional areas by 62% (P < 0.05). High-lycopene supplementation also decreased the positive rate of proliferating cellular nuclear antigen (PCNA), the level of VEGF, and protein expressions of PCNA, MMP-9, and VEGF in lung tissues. However, high-lycopene increased the protein expression of nm23-H1 (an antimetastatic gene) by 133% (P < 0.001). For most variables measured, effects of lycopene were dose dependent and the effect of beta-carotene was between those of high-dose and low-dose lycopene. These results show that lycopene supplementation reduces experimental tumor metastasis in vivo and suggest that such an action is associated with attenuation of tumor invasion, proliferation, and angiogenesis.
Huang
Chin-Shiu
CS
Department of Food Science and Biotechnology, National Chung-Hsing University, Taichung 40227, Taiwan.
Liao
Jiunn-Wang
JW
Hu
Miao-Lin
ML
D000818:Animals; D001835:Body Weight; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology*; D002338:Carotenoids / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004032:Diet; D019587:Dietary Supplements; D005786:Gene Expression Regulation; D006801:Humans; D018664:Interleukin-12 / Q000097:blood; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D000077276:Lycopene; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D051379:Mice; D008819:Mice, Nude; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D009374:Neoplasms, Experimental; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000378:metabolism; D019207:beta Carotene / Q000378:metabolism
D054778:NM23 Nucleoside Diphosphate Kinases; D018809:Proliferating Cell Nuclear Antigen; D042461:Vascular Endothelial Growth Factor A; D019207:beta Carotene; D018664:Interleukin-12; D002338:Carotenoids; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000077276:Lycopene