Curcumin blocks migration and invasion of mouse-rat hybrid retina ganglion cells (N18) through the inhibition of MMP-2, -9, FAK, Rho A and Rock-1 gene expression.
Cancer metastasis involves multiple processes which may complicate clinical management and even lead to death. Matrix metalloproteinases (MMPs) play an important role in cancer cell invasion, metastasis and angiogenesis, depending on whether agents can inhibit MMPs which could lead to inhibition of the migration and invasion of cancer cells. Curcumin, the active constituent of the dietary spice turmeric, has potential for the prevention and therapy of cancer. However, there is no study to address the effects of curcumin on migration and invasion of mouse-rat hybrid retina ganglion cells (N18). This is the first study to explore the anti-migration and -invasion of curcumin in mouse-rat hybrid retina ganglion cells (N18) in vitro. Curcumin exerted a dose- and time-dependent inhibitory effect on the invasion and migration of N18 cells in vitro. Results from Western blotting showed that curcumin inhibited the protein levels of PKC, FAK, NF-kappaB p65 and Rho A leading to the inhibition of ERK1/2, MKK7, COX-2 and ROCK1, respectively, finally causing the inhibition of MMP-2 and -9 for the inhibition of migration and invasion of N18 cells. Moreover, this action was involved in the inhibition of gene expression of MMP-2 and -7, FAK, ROCK1 and Rho A. Overall, the above data show that the anticancer effect of curcumin also exists for the inhibition of migration and invasion in N18 cells, and that curcumin may be a powerful candidate for developing preventive agents for cancer metastasis.
Lin
Hui-Ju
HJ
Department of Ophthalmology, China Medical University Hospital, Taichung 404, Taiwan.
Su
Chin-Cheng
CC
Lu
Hsu-Feng
HF
Yang
Jai-Sing
JS
Hsu
Shu-Chun
SC
Ip
Siu-Wan
SW
Wu
Jia-Jiuan
JJ
Li
Yu-Ching
YC
Ho
Chin-Chin
CC
Wu
Chih-Chung
CC
Chung
Jing-Gung
JG
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002465:Cell Movement; D003474:Curcumin / Q000494:pharmacology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D006822:Hybrid Cells; D008223:Lymphoma / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000502:physiology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors* / Q000235:genetics
D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D051416:Focal Adhesion Protein-Tyrosine Kinases; D054460:rho-Associated Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020742:rhoA GTP-Binding Protein; D003474:Curcumin