Tumor invasion into extracellular matrix (ECM) and basement membrane (BM) is a crucial step in the complex multistage process that leads to
metastasis formation. GG6-10
galloylglucose, isolated from
Galla Rhois, inhibited the invasion of metastatic HT-1080 cells into a reconstituted BM, such as a
Matrigel/
fibronectin (FN)-coated filter, in a concentration-dependent fashion. GG6-10 affected neither the
tumor cell adhesion and haptotactic migration to ECM components (
Matrigel and FN), nor the growth of HT-1080 cells. The
gelatin zymography revealed that GG6-10 was able to inhibit not only the degradation of
gelatin mediated by
matrix metalloproteinases (MMP)-2 and -9 in
conditioned medium of HT-1080
tumor cells but also the production of
MMP from the
tumor cells in a concentration-dependent manner.
MMP production is well known to be positively regulated by various
cytokines, such as
tumor necrosis factor-alpha (
TNF-alpha). Thus, we examined the effect of GG6-10 on the
TNF-alpha-mediated translation of the MMP-9 gene using HT-1080 cells transfected with the MMP-9 promoter linked to the
luciferase gene as a reporter. Similarly to
prednisolone, GG6-10 was found to inhibit the
TNF-alpha-inducible promoter activity. In keeping with these results, GG6-10 might inhibit
tumor cell invasion by inhibiting the gelatinolysis mediated by MMP-2 and -9 and interfering with the production of
MMP via inhibiting transcription of the promoter for
MMP.