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

J Biochem Mol Toxicol. 2020 Aug;34(8):e22514. doi: 10.1002/jbt.22514. Epub 2020 May 2.


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.

Keywords: JAK/STAT pathway; MG-63 cells; ROS; apoptosis; inflammation; β-caryophyllene.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • DNA Fragmentation / drug effects*
  • Humans
  • Janus Kinase 1 / metabolism*
  • Mice
  • Neoplasm Proteins / metabolism*
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology
  • Polycyclic Sesquiterpenes / pharmacology*
  • Reactive Oxygen Species / metabolism*
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects


  • Neoplasm Proteins
  • Polycyclic Sesquiterpenes
  • Reactive Oxygen Species
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • caryophyllene
  • JAK1 protein, human
  • Janus Kinase 1