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.