JAK1/STAT3 regulatory effect of β-caryophyllene on MG-63 osteosarcoma cells via ROS-induced apoptotic mitochondrial pathway by DNA fragmentation.

Abstract

Currently, available treatment for osteosarcoma is combinational chemotherapy of doxorubicin, cisplatin, and methotrexate before and after surgery with overall 5-year survival rate of less than 40%. The present study was aimed to assess the anticancer effects of a phytochemical named β-caryophyllene (BCP) in treating osteosarcoma. We assessed the effect of (BCP) on oxidative stress, proliferation, apoptosis, and inflammation in human bone cancer cells MG-63. Our results showed that BCP induced reactive oxygen species (ROS) generation at 20 µM concentration in MG-63 cells. The same dose was also shown to exhibit proapoptotic and antiproliferative effects in bone cancer cells MG-63. We demonstrated that the treatment of MG-63 cells with BCP prompted mitochondrial apoptosis via upregulation of Bax and caspase-3 and downregulation of Bcl-2 as well as prompted mitochondrial membrane potential. Our results also showed stimulation of Janus kinase 1/signal transducer and activator of transcription 3 (JAK1/STAT3) signaling pathway in bone cancer MG-63 cells upon BCP treatment along with the induction of proinflammatory genes at the messenger RNA level. Overall results suggest that the treatment of MG-63 cells with BCP promotes apoptosis and inflammation via ROS and JAK1/STAT3 signaling pathway.