Anti-metastatic activity of an apple polyphenol crude fraction against human Ha ras-transformed metastatic mouse tumor (r/m HM-SFME-1) cells

Summary Oral administration of a 0.5% crude fraction of an apple polyphenol significantly inhibited the spontaneous lung metastasis of r/m HM-SFME-1 tumor cells, but did not significantly inhibit tumor growth at the site of transplantation. This fraction dose-dependently inhibited the in vitro invasion and migration of the tumor, and inhibited slightly the MMP-9 production and IFN-γ plus LPS-augmented VEGF gene expression of the tumor, although non-augmented VEGF gene expression was stimulated in a dose-dependent fashion by the fraction. In addition, the polyphenol fraction inhibited the MMP-9 production of the fibroblast cell line NIH3T3, but not that of the macrophage cell line J774.1, and inhibited the VEGF gene expression of both stromal cell types. NO production by J774.1 cells was also inhibited significantly. These findings indicate that the anti-metastatic activity of the crude polyphenol fraction occurs via the inhibition of both tumor and stromal cell activities. It is noteworthy that the anti- metastatic activity of the polyphenol fraction occurs in the absence of any direct inhibition of tumor growth.