Sanguinarine induces apoptosis of human osteosarcoma cells through the extrinsic and intrinsic pathways

The quaternary benzo[c]phenanthridine alkaloid sanguinarine inhibits the proliferation of cancerous cells from different origins, including lung, breast, pancreatic and colon, but nothing is known of its effects on osteosarcoma, a primary malignant bone tumour. We have found that sanguinarine alters the morphology and reduces the viability of MG-63 and SaOS-2 human osteosarcoma cell lines in concentration- and time-dependent manner. Incubation with 1 μmol/L sanguinarine for 4 and 24 h killed more efficiently MG-63 cells than SaOS-2 cells, while incubation with 5 μmol/L sanguinarine killed almost 100% of both cell populations within 24 h. This treatment also changed the mitochondrial membrane potential in both MG-63 and SaOS-2 cells within 1 h, caused chromatin condensation and the formation of apoptotic bodies. It activated multicaspases, and increased the activities of caspase-8 and caspase-9 in both MG-63 and SaOS-2 cells. These data highlight sanguinarine as a novel potential agent for bone cancer therapy.

Research highlights
► We show for the first time the effect of sanguinarine (SA) on MG63 and SaOS-2 cells.
► SA altered osteosarcoma cell viability in a concentration and time dependent manner.
► SA induced osteosarcoma cell apoptosis and increased caspase-8 and -9 activities.
► SA decreased dose dependently the Bcl-2 protein level only in MG63 cells.
► SaOS-2 which are osteoblast-derived, seemed more resistant to SA than MG63.