Elemene inhibits osteosarcoma growth by suppressing the renin-angiotensin system signaling pathway

Osteosarcoma remains the most prevalent primary malignant bone tumor in children and young adults globally. Therefore, novel and highly effective antitumor agents are urgently required. Elemene is a natural plant compound extracted from the medicinal Chinese herb, Rhizomazedoariae, which has been employed as an antitumor agent for the treatment of a number of tumors, including osteosarcoma. However, the mechanisms underlying its antitumor effect are currently unclear. The human osteosarcoma cell lines, MG-63 and U2OS, were employed in the present study. MTT, migration, transwell invasion and terminal deoxynucleotidyltransferase-mediated deoxy-UTP-fluorescein nick end-labeling assays were performed to evaluate cell viability, migration, invasion and apoptosis, respectively. Western blotting and immunohistochemistry analyses were performed to measure the levels of renin-angiotensin system (RAS) components. In order to evaluate the effect of elemene on tumor weight and volume, MG-63 and U2OS cells were injected into mice. Treatment of osteosarcoma cell lines, MG-63 and U2OS, with elemene led to the inhibition of cell viability, migration and invasion, as well as induction of cell apoptosis. In addition, elemene treatment downregulated the expression of a number of RAS components. The growth of osteosarcoma cell-transplanted tumors in nude mice and angiotensin II expression were inhibited by elemene treatment. The results of the present study indicate that the antitumor effects of elemene may partly be due to downregulation of the RAS signaling pathway, and that RAS may be a putative pharmacological target for osteosarcoma therapy.