Curcumin exhibits antimetastatic properties by modulating integrin receptors, collagenase activity, and expression of Nm23 and E-cadherin.
Curcumin (diferuloyl methane), the major pigment from the rhizome of Curcuma longa L., has been widely studied for its tumor-inhibiting properties. Recent studies indicate that curcumin can modify cell receptor binding, it also affects intracellular signalling reactions. Curcumin-treated B16F10 melanoma cells formed eight-fold fewer lung metastases in C57BL6 mice. In the cell adhesion assays, curcumin-treated cells showed a dose-dependent reduction in their binding to four extracellular matrix (ECM) proteins. The binding to fibronectin, vitronectin, and collagen IV decreased by over 50% in 24 hours, and by 100% after 48 hours of curcumin treatment, it persisted at this level even after 15 days of cultivating cells in curcumin-free medium. Curcumin-treated cells showed a marked reduction in the expression of alpha5beta1 and alpha(v)beta3 integrin receptors. In addition, curcumin treatment inhibited pp125 focal adhesion kinase (FAK), tyrosine phosphorylation of a 120 kD protein, and collagenase activity. Curcumin enhances the expression of antimetastatic proteins, tissue inhibitor metalloproteinase (TIMP)-2, nonmetastatic gene 23 (Nm23), and E-cadherin. In this article we report on the effect of curcumin on the expression of integrin, TIMP-2, Nm23, E-cadherin, adhesion, and metalloproteinase activity.
Ray
Subrata
S
Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Calcutta, India.
Chattopadhyay
Nibedita
N
Mitra
Aparna
A
Siddiqi
Maqsood
M
Chatterjee
Amitava
A
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015820:Cadherins / Q000096:biosynthesis*; D002448:Cell Adhesion / Q000187:drug effects; D017364:Collagenases / Q000187:drug effects / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016023:Integrins / Q000378:metabolism*; D008175:Lung Neoplasms / Q000556:secondary*; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000473:pathology*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D015820:Cadherins; D016023:Integrins; D019717:Tissue Inhibitor of Metalloproteinase-3; D017364:Collagenases; D003474:Curcumin