Sulforaphane enhances cisplatin sensitivity in human osteosarcoma cells through upregulation of p53-p21 pathway by enhancing G1 arrest

Background: Cisplatin (CisPt) resistance is one of the major problems for the treatment of osteosarcoma. The natural compound sulforaphane (SFN) are reported to have antitumor activity in many cancers. However, its effect to influence CisPt resistance in osteosarcoma cells has not examined. In this study, we intended to investigate the combined effects of SFN and CisPt in osteosarcoma cells and to investigate the related mechanism. Methods: Human osteosarcoma OS-732 and MG-63 cells were treated with SFN or cisplatin (cisPt) or combination of both for 72 h. The cell survival rate was measured by MTT assay. The cell cycle distribution and cell death were measured by flow cytometry. The expression of cell cycle and apoptosis related genes were analyzed by qRT-PCR and western blot. Results: The combination of SFN and CisPt had significantly greater cell growth inhibitory effects than either treatment alone. The combined treatment of SFN and CisPt increased the population of cells in the G1 phase and cell death than SFN or CisPt alone. The combination of SFN and CisPt treatment increased the expression of p53, p27, p21 and Bax and decreased the expression of cyclin D and E as compared to SFN or CisPtalone treatment. Conclusion: Taken together, we demonstrate that SFN enhanced CisPt sensitivity of osteosarcoma cells by inducing apoptosis through G1-phase arrest and by activating tumor suppressor p53-p21 pathway, suggesting that SFN may be used as a chemosensitizer for osteosarcoma treatment.