Anti-tumor efficacy of phellamurin in osteosarcoma cells: Involvement of the PI3K/AKT/mTOR pathway

The extracts of Phellodendron amurense (P. amurense) have been shown to contain many active ingredients e.g. flavone glycosides and to exert a wide range of physiological activities including anti-tumor activity. However, the effects of phellamurin (Phe), a plant flavonone glycoside from the leaves of P. amurense, on osteosarcoma (OS) have never been reported. The effects of Phe on cell viability and apoptosis were evaluated by MTT assay and flow cytometry analysis, respectively. Western blot analysis was performed to detect the protein levels of phosphorylated phosphatidylinositol 3 kinase (PI3K) (p-PI3K), phosphorylated protein kinase B (AKT) (p-AKT), AKT, phosphorylated mammalian target of rapamycin (mTOR) (p-mTOR), and mTOR. We found that Phe suppressed the viability and promoted apoptosis in OS cells in a dose-dependent manner. Notably, Phe repressed the PI3K/AKT/mTOR pathway in OS cells. LY294002 effectively inhibited the PI3K/AKT/mTOR signaling pathway, repressed cell viability and induced apoptosis in OS cells. Activation of PI3K/AKT/mTOR pathway by 740Y-P abolished the effects of Phe on the viability and apoptosis of OS cells. We also found that Phe repressed OS tumor growth and inhibited the PI3K/AKT/mTOR pathway in vivo. In conclusion, Phe suppressed the viability and induced apoptosis in OS cells, at least, partially by inhibiting the PI3K/AKT/mTOR pathway. Our study suggested that Phe might be a new and potential chemotherapeutic agent for the treatment of OS.