Picroside II, an iridoid glycoside from Picrorhiza kurroa, suppresses tumor migration, invasion, and angiogenesis in vitro and in vivo

Abstract

Cancer is one of the leading causes of death worldwide. The development of novel anti-cancer agents from natural products is a promising approach to reduce cancer mortality. In this study, we investigated the anti-metastatic and anti-angiogenic activities of picroside II (PII) in human breast cancer cells both in vitro and in vivo. Our results demonstrated that PII significantly inhibited the migration and invasion of MDA-MB-231 cancer cells. With the treatment of PII, the activity of matrix metalloproteinase 9 (MMP-9) in MDA-MB-231 cancer cells was significantly inhibited both in vitro and in vivo. Meanwhile, PII showed effective anti-metastatic activity in an experimental lung metastasis model. Interestingly, cluster of differentiation 31 (CD31), a marker of angiogenesis, was significantly downregulated in the PII-treated tumor samples, indicating the anti-angiogenic activity of PII. Furthermore, we demonstrated that PII significantly inhibited the migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs). The inhibition of MMP-9 activity in PII-treated HUVECs was also demonstrated. Finally, the suppression of angiogenesis by PII in the chick embryo chorioallantoic membrane (CAM) was observed. In conclusion, our results demonstrated that PII effectively inhibited the metastasis and angiogenesis of cancer cells both in vitro and in vivo, and thus, might be a novel candidate for cancer therapy.