Ascorbic acid induces either differentiation or apoptosis in MG-63 osteosarcoma lineage.

Osteosarcoma originates from mesenchymal stem cells with impaired bone differentiation. In the present study we investigated the effect of ascorbic acid (AsA) on osteogenic differentiation and apoptosis of the MG-63 osteosarcoma cell line. We evaluated the expression of runt-related transcription factor-2 (RUNX2) and secreted phosphoprotein 1 (SPP1) genes by real-time Polymerase Chain Reaction (PCR) and of endogenous bone morphogenetic protein-2 (BMP2) and osteocalcin proteins by immunohistochemistry. We analyzed osteoblast maturation by phosphatase alkaline synthesis and calcium deposition, and apoptosis by (TUNEL) test and Annexin staining. Our results showed that RUNX2 and SPP1 gene expression was increased in cells treated with low concentrations of AsA with respect to untreated cells. At higher concentrations, AsA induced apoptosis of osteosarcoma cells, possibly with the involvement of p21. Our findings support the ability of AsA to induce both differentiation, by affecting the target involved in early and late phases of osteogenic maturation, and apoptosis in poorly-differentiated osteosarcoma cells.