Magnolol induces apoptosis in osteosarcoma cells via G0/G1 phase arrest and p53-mediated mitochondrial pathway

J Cell Biochem. 2019 Oct;120(10):17067-17079. doi: 10.1002/jcb.28968. Epub 2019 Jun 3.

Abstract

Osteosarcoma is a highly invasive primary malignancy of bone. Magnolol is biologically active, which shows antitumor effects in a variety of cancer cell lines. However, it has not been elucidated magnolol's effects on human osteosarcoma cells (HOC). This study aimed to determine antitumor activity of magnolol and illustrate the molecular mechanism in HOC. Magnolol showed significant inhibition effect of growth on MG-63 and 143B cells and induced apoptosis and cell cycle arrest at G0/G1. In osteosarcoma cells, magnolol upregulated expressions of proapoptosis proteins and suppressed expressions of antiapoptosis proteins. Additionally, under the pretreatment of pifithrin-a (PFT-a, a p53 inhibitor), the magnolol-induced apoptosis was significantly reversed. The results above indicated that magnolol induces apoptosis in osteosarcoma cells may via G0/G1 phase arrest and p53-mediated mitochondrial pathway.

Keywords: apoptosis; magnolol; mitochondria; osteosarcoma; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Biphenyl Compounds / pharmacology*
  • Cell Line, Tumor
  • Cyclin D1 / antagonists & inhibitors
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase 2 / antagonists & inhibitors
  • Cyclin-Dependent Kinase 2 / genetics
  • Cyclin-Dependent Kinase 2 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / agonists
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • G1 Phase Cell Cycle Checkpoints / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lignans / pharmacology*
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Mitochondrial Membrane Transport Proteins / agonists
  • Mitochondrial Membrane Transport Proteins / genetics
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Mitochondrial Permeability Transition Pore
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Osteoblasts / pathology
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / agonists
  • Reactive Oxygen Species / metabolism
  • Resting Phase, Cell Cycle / drug effects
  • Resting Phase, Cell Cycle / genetics
  • Signal Transduction
  • Tumor Suppressor Protein p53 / agonists
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-2-Associated X Protein / antagonists & inhibitors
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • BAX protein, human
  • BCL2 protein, human
  • Biphenyl Compounds
  • CCND1 protein, human
  • Lignans
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Permeability Transition Pore
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • magnolol
  • Cyclin D1
  • Cyclin-Dependent Kinase Inhibitor p27
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2