Alpinetin suppresses cell proliferation and metastasis in osteosarcoma by inhibiting PI3K/AKT and ERK pathways

Abstract

Alpinetin, a natural flavonoid found in medicinal herbs, possesses distinct pharmacological activities, including neuroprotective, antiviral, antibacterial, lung and cardiovascular protective, hepatoprotective, antiinflammatory, and antitumor properties. Here, the role of alpinetin was investigated in osteosarcoma. Osteosarcoma cell lines (143B and U2OS) were treated with 10-, 25-, 50-, 75-, or 100-μM concentration of alpinetin. Cell proliferation was detected by cell counting kit 8 (CCK8) and colony formation assays. Western blotting and flow cytometry were used to investigate cell apoptosis. Cell metastasis was assessed by transwell assay. Administration of alpinetin reduced the viabilities of 143B and U2OS cell lines in a dosage-dependent manner, and decreased the number of colonies of 143B and U2OS cell lines. The apoptosis of 143B and U2OS cell lines was promoted by alpinetin through down-regulation of Bcl-2 and up-regulation of cleaved caspase-3 and Bax. Alpinetin inhibited invasion and migration of 143B and U2OS cell lines through up-regulation of epithelial biomarkers, E-cadherin, and zonula occludens-1 (ZO-1), and down-regulation of mesenchymal biomarkers, Vimentin, and N-cadherin. Alpinetin also reduced the phosphorylation of extracellular signal-regulated kinase (ERK), Ak strain transforming (AKT), and phosphoinositide 3-kinases (PI3K) in 143B and U2OS cell lines. Alpinetin inhibited cell proliferation and metastasis in osteosarcoma through inactivation of PI3K/AKT and ERK pathways, providing potential treatment option for treatment of cancer.