Prevention of intrahepatic metastasis by curcumin in an orthotopic implantation model.
Curcumin has been shown to have potent anti-metastatic activity, however, its mechanism of action is still unclear. Here, we analyzed the anti-metastatic mechanism using hepatocellular carcinoma, CBO140C12 cells. Daily oral administration of curcumin suppressed intrahepatic metastasis in a dose-dependent manner, whereas the growth of implanted tumors was not affected. We next examined the effect of curcumin on several metastatic properties in vitro. Curcumin inhibited the invasion of tumor cells through Matrigel-coated filters and the production of MMP-9. In addition, curcumin significantly inhibited adhesion and haptotactic migration to fibronectin and laminin without affecting the expression of integrins on the cell surface. Furthermore, the formation of actin stress fibers was affected by treatment with curcumin. These results suggested that curcumin suppressed the intrahepatic metastasis mediated by the inhibiton of several metastatic properties, in which the functional alteration of cytoskeletal organization, at least in part, could play an important role.
Ohashi
Yasukata
Y
Department of Pathogenic Biochemistry, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
Tsuchiya
Yasunori
Y
Koizumi
Keiichi
K
Sakurai
Hiroaki
H
Saiki
Ikuo
I
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003474:Curcumin / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control* / Q000556:secondary; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D013047:Specific Pathogen-Free Organisms; D014407:Tumor Cells, Cultured / Q000637:transplantation
D000970:Antineoplastic Agents; D020780:Matrix Metalloproteinase 9; D003474:Curcumin