Abstract
The current study was aimed to evaluate the anti-proliferative activity of nobiletin, a flavonoid, on osteosarcoma cell line, SaOS-2. Furthermore, we attempted to investigate the signaling pathways involved in the cell growth inhibition mechanism. Upon exposure, nobiletin showed significant cell inhibitory effect on SaOS-2 cells in a dose dependent manner as evidenced by MTT assay and LDH assay. Moreover, flow cytometric analysis demonstrated that upon treatment with nobiletin, SaOS-2 cells underwent apoptosis and showed increased number of cells arrested in G2/M phase. Activation of caspase-9 and -3 indicate the activation of apoptotic signaling pathway in SaOS-2 cells. Additionally, it was observed that the cell inhibitory effect was regulated by the activation of ERK signaling pathway while AKT signaling pathway was down regulated in SaOS-2 cells after 24 h of Nobiletin treatment.
Highlights
Skeletal integrity is maintained by equilibrium between osteoblasts mediated bone formation and osteoclasts mediated bone resorption
To examine whether nobiletin treatment could affect cellcycle progression and apoptosis in osteosarcoma cells, SaOS-2 cells were treated with different concentrations of nobiletin
Rate of apoptosis and phase of cell cycle arrest induced by nobiletin on SaOS-2 cells was analyzed using flow cytometry after 24 hours of treatment
Summary
Skeletal integrity is maintained by equilibrium between osteoblasts mediated bone formation and osteoclasts mediated bone resorption. Any imbalance in this equilibrium leads to osteoblastic lesions and other severe clinical consequences often termed as bone cancer or osteosarcoma. Bone cancer is resulted by invasion of different cancers to bone tissue, phenomenon known as bone metastases. American cancer society estimates nearly 3,020 new cases of bone cancer and 1,460 deaths due to bone cancer in 2014 (American Cancer Society, 2014). Over the past few years, the development of natural compounds as anticancer agents has been revealed (Newman and Cragg, 2007). Intensive efforts for discovering new drugs based on natural products has proven beneficial, with nearly
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