lthough there are many therapeutic strategies such as surgery and chemotherapy

the prognosis of osteosarcoma (OS) is still far from being satisfactory. It is urgent to develop more effective

tolerable and safe drugs for the treatment of OS. In the present study

we investigated the anti-OS activity of Alantolactone (ALT)

a natural eucalyptone sesquiterpene lactone mainly exists in Inula helenium

and probed the possible mechanism involved. We demonstrated that ALT significantly inhibited cell proliferation of various human OS cell lines while had relative lower cytotoxicity against normal cells. Then

we validated that ALT reduced migration

decreased invasion possibly through reversing epithelial mesenchymal transition (EMT) process and suppressing Matrix metalloproteinases (MMPs). Moreover

we confirmed that ALT promoted apoptosis and arrested cell cycle at G2/M phase of human OS cells

in vitro

. In addition

we confirmed that ALT restrained tumor growth and metastasis of OS 143 cells in a xenograft model

in vivo

. Mechanistically

ALT inhibited the activity of Wnt/β-catenin and p38

ERK1/2 and JNK Mitogen Activated Protein Kinases (MAPKs) signal pathway. Notably

the combination of ALT and Wnt/β-catenin inhibitor

as well as the combination of ALT and MAPKs inhibitors resulted in a synergistically effect on inhibiting the proliferation

migration and invasion of OS cells. Collectively

our results validate the ALT may inhibit proliferation

metastasis and promotes apoptosis of human OS cells possibly through suppressing Wnt/β-Catenin and MAPKs signaling pathways.