279

Recent evidence suggests that multiple cross talk among tumor cells and various host cells trigger the metastatic pathways. However, there are no drugs available to inhibit the metastasis of cancer cells. Accordingly, there have been many studies aimed at screening natural products for their anti-metastatic potentials. Xanthorrhizol is a sesquiterpenoid compound from the rhizome of Curcuma xanthorrhiza and is widely used as a traditional medicine in Indonesia. Therefore, this study used an in vivo mouse lung metastasis model (using a tail vein injection of a murine colon cancer cell line, CT26, onto Balb/c mice) and a tumor mass formation assay (using an intraperitoneal (i.p.) injection of a metastatic melanoma cell, B16BL6, onto C57BL6 mice) to evaluate the anti-metastatic activity of xanthorrhizol. Interestingly, xanthorrhizol inhibited the intra-abdominal tumor masses formation and the formation of tumor nodules in the lung tissue. These results suggested that xanthorrhizol possesses anti-metastatic activity in vivo. In order to examine the mechanism of the anti-metastatic action of xanthorrhizol in the mouse lung metastasis model, the expression pattern of several intracellular signaling molecules with the lung tissues including tumor nodules were evaluated. Higher expression levels of COX-2, MMP-9, p-ERK, Akt, and procaspase-9 in the metastatic group were observed, but these were attenuated by a treatment with xanthorrhizol. Furthermore, xanthorrhizol exhibited anti-proliferation and pro-apoptotic activity in colon cancer cells via the inhibition of the cell proliferation, the induction of the DNA fragmentation and the morphological changes in xanthorrhizol-treated cancer cells. Overall, xanthorrhizol exerts its anti-metastatic activity in vivo and its anti-cancer activity in vitro via the metastasis-related multiplex signal pathway.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]