Crude extract of Rheum palmatum inhibits migration and invasion of U-2 OS human osteosarcoma cells by suppression of matrix metalloproteinase-2 and -9

Osteosarcoma is the most common primary bone malignancy and primarily occurs in adolescents and young adults. Crude extract of Rheum palmatum L. (CERP) has been used as a traditional Chinese medicine for different diseases and there is experimental evidence that it may have anti-cancer effects. However, there is no information showing that CERP can affect the mobility of human osteosarcoma cells. In this study we determined the effects of CERP on U-2 OS human osteosarcoma cells. We found that CERP significantly inhibited the migration and invasion of U-2 OS cells. CERP also reduced the activity of matrix metalloproteinase (MMP)-2 and MMP-9 and decreased expression levels of the proteins FAK, GRP78, PKC, HIF-1, SOS1, VEGF, PI3K, GRB2, Ras, p-ERK1/2, ERK1/2, p-p38, JNK1/2, p-JNK1/2, MEKK3, MKK7, PERK, p-PERK, iNOS, COX-2, NF-κB p65, IRE-1, UPA, and RhoA in U-2 OS cells. Confocal laser microscopy revealed that CERP decreased the expression of NF-κB p65, RhoA and Rock 1. These in vitro studies suggest that CERP may have novel anti-cancer actions in the treatment of osteosarcoma. Further studies including animal models of bone cancer are warranted.