Curcumin inhibits tumor growth and angiogenesis in glioblastoma xenografts.
Among the natural products shown to possess chemopreventive and anticancer properties, curcumin is one of the most potent. In the current study, we investigated the effects of this natural product on the growth of human glioma U-87 cells xenografted into athymic mice. We show here that curcumin administration exerted significant anti-tumor effects on subcutaneous and intracerebral gliomas as demonstrated by the slower tumor growth rate and the increase of animal survival time. While investigating the mechanism of its action in vivo, we observed that curcumin decreased the gelatinolytic activities of matrix metalloproteinase-9. Furthermore, treatment with curcumin inhibited glioma-induced angiogenesis as indicated by the decrease of endothelial cell marker from newly formed vessels and by the diminution of the concentration of hemoglobin in curcumin-treated tumors. We also demonstrate, using an in vitro model of blood-brain barrier, that curcumin can cross the blood-brain barrier to a high level. These are the first results showing that curcumin suppresses tumor growth of gliomas in xenograft models. The mechanisms of the anti-tumor effects of curcumin were related, at least partly, to the inhibition of glioma-induced angiogenesis.
Perry
Marie-Claude
MC
Laboratoire de médecine moléculaire, Université du Québec à Montréal- Hôpital Sainte-Justine, Montréal, Canada. perry.marie-claude@courrier.uqam.ca
Demeule
Michel
M
Régina
Anthony
A
Moumdjian
Robert
R
Béliveau
Richard
R
D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D016588:Anticarcinogenic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001812:Blood-Brain Barrier / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003474:Curcumin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005909:Glioblastoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D051381:Rats; D016019:Survival Analysis; D057900:Transcytosis; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D016588:Anticarcinogenic Agents; D000972:Antineoplastic Agents, Phytogenic; D061965:Matrix Metalloproteinase Inhibitors; D003474:Curcumin