Apiosporamide, A 4-hydroxy-2-pyridone Alkaloid, Induces Apoptosis Via PI3K/Akt Signaling Pathway In Osteosarcoma Cells

Background: Osteosarcoma (OS) is a common primary malignant bone tumour in children and young adults. Apiosporamide, a 4-hydroxy-2-pyridone alkaloid from a deep-sea-derived fungus, Arthrinium sp. UJNMF0008, showed anti-proliferative effects toward a panel of human cancer cell lines, and the molecular mechanism in MG63 cells was then investigated in the current work. Methods: Cell viability was determined with MTT method. Cell proliferation was detected using colony-formation assay. Screening electron microscope was used for morphology observation. Cell cycle and apoptosis was analysed via flow cytometry. Real-time PCR was conducted to evaluate the mRNA expression related with cell apoptosis. The expression levels of proteins related to capase-mediated apoptotic pathway and PI3K/Akt signalling pathway were detected by Western blotting. Results: Apiosporamide significantly decreased cell viability in cancer cells, and also exhibited excellent anti-proliferative effect. Apiosporamide caused cell cycle arrests at G0/G1 phase in MG63 cells. Moreover, apiosporamide induced apoptosis, activated caspase-3, caspase-8 and caspase-9, and regulated expression of Bax and Bcl-2 in MG63 cells. In addition, apiosporamide also attenuated PI3K/Akt signaling pathway. Conclusion: Apiosporamide effectively suppressed MG63 cells proliferation by inducing apoptosis through PI3K/Akt and caspase-associated apoptotic pathway.