OncoTargets and Therapy (Oct 2019)
Apiosporamide, A 4-hydroxy-2-pyridone Alkaloid, Induces Apoptosis Via PI3K/Akt Signaling Pathway In Osteosarcoma Cells
Abstract
Yuying Zhang,1 Qianqian Zhang,1 Jie Bao,1 Jintian Huang,2 Hua Zhang1 1Department of Biotechnology, School of Biological Science and Technology, University of Jinan, Jinan 250022, People’s Republic of China; 2Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, People’s Republic of ChinaCorrespondence: Hua ZhangDepartment of Biotechnology, School of Biological Science and Technology, University of Jinan, 336 West Road of Nan Xinzhuang, Jinan 250022, People’s Republic of ChinaTel +86 531 8973 6199Email [email protected]: 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.Keywords: apiosporamide, osteosarcoma, anti-proliferation, apoptosis, PI3K/Akt
