Anti-invasive activity of torilin, a sesquiterpene compound isolated from Torilis japonica

Torilin is a sesquiterpene compound purified from Torilis japonica (Umbelliferae). We have previously reported that torilin has a potent anti-angiogenic activity both in vivo and in vitro. In the present study, we investigated the anti-invasive activity of torilin, and interestingly found that torilin completely blocked intravasation of HT1080 human fibrosarcoma cells inoculated on the chorioallantoic membrane (CAM) of chick embryo. In addition, torilin decreased the attachment of HT1080 cells to confluent human umbilical vein endothelial cells (HUVECs) at non-toxic concentration. In in vitro transwell invasion model, 25 microM torilin also significantly inhibited HT1080 cell invasion in a time-dependent manner. Activity and expression of matrix metalloproteinase-9 (MMP-9) that is very important in tumor invasion and metastasis were also decreased by torilin treatment, indicating that the inhibitory effect of torilin on invasion of HT1080 cells may result from decreasing activity and expression of MMP-9. Therefore, it is possible that torilin may decrease metastatic potential of tumor cells through inhibiting their attachment to endothelial cells and intravasation to blood vessels. Taken together, torilin may have a strong activity to suppress tumorigenesis by inhibition of tumor invasion.