Effects of curcumin on tumor angiogenesis and biomarkers, COX-2 and VEGF, in hepatocellular carcinoma cell-implanted nude mice.
Anti-angiogenic activity of curcumin and effects of curcumin on angiogenic biomarkers, cycloxygenase (COX)-2 and vascular endothelial growth factor (VEGF) levels were investigated. One day after hepatocellular carcinoma cell (HepG2) cells (30 microl of 2 x 10(6) cells) were inoculated onto the upper layer of the skin-fold chamber (HepG2-group, n = 15), curcumin solutions of 300 and 3000 mg/kg BW were daily oral fed to HepG2-Cur-300 and HepG2-Cur-3000 groups (n = 30), respectively. Intravital fluorescence videomicroscopy was performed to monitor neocapillaries in the tumor on days 3, 7 and 14 post-tumor-inoculation, using RITC-dextran (0.1 ml of 0.5% injected intravenously). The tumor neocapillary density (NCD) was evaluated in correlation with the tumor area, using a digital image analysis. The results demonstrated that the NCD of HepG2-groups were significantly increased on day 7 and 14, compared to the aged-matched Sham-groups (p<0.001). The increased NCD on day 7 and 14 were attenuated significantly by daily treatment of curcumin solution (3000 mg/kg BW).The curcumin treatment reduced the tumor-induced over-expression of COX-2 and serum VEGF in HepG2 groups significantly (p<0.001), indicating that curcumin could inhibit tumor angiogenesis. This mechanism might be mediated through reduction of angiogenic biomarkers, COX-2 and VEGF.
Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Pornprom
P
Yoysungnoen
Porntip
P
Wirachwong
Pavaphon
P
Bhattarakosol
Hideyuki
H
Niimi
Suthiluk
S
Patumraj
D020533:Angiogenesis Inhibitors; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000188:drug therapy*; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D018715:Microscopy, Video; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D020533:Angiogenesis Inhibitors; D015415:Biomarkers; D008565:Membrane Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D003474:Curcumin