Magnolol inhibits growth of gallbladder cancer cells through the p53 pathway

Cancer Sci. 2015 Oct;106(10):1341-50. doi: 10.1111/cas.12762.

Abstract

Magnolol, the major active compound found in Magnolia officinalis has a wide range of clinical applications due to its anti-inflammation and anti-oxidation effects. This study investigated the effects of magnolol on the growth of human gallbladder carcinoma (GBC) cell lines. The results indicated that magnolol could significantly inhibit the growth of GBC cell lines in a dose- and time-dependent manner. Magnolol also blocked cell cycle progression at G0 /G1 phase and induced mitochondrial-related apoptosis by upregulating p53 and p21 protein levels and by downregulating cyclin D1, CDC25A, and Cdk2 protein levels. When cells were pretreated with a p53 inhibitor (pifithrin-a), followed by magnolol treatment, pifithrin-a blocked magnolol-induced apoptosis and G0 /G1 arrest. In vivo, magnolol suppressed tumor growth and activated the same mechanisms as were activated in vitro. In conclusion, our study is the first to report that magnolol has an inhibitory effect on the growth of GBC cells and that this compound may have potential as a novel therapeutic agent for the treatment of GBC.

Keywords: Apoptosis; cell cycle arrest; gallbladder carcinoma; magnolol; p53 pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Biphenyl Compounds / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclin D1 / biosynthesis
  • Cyclin-Dependent Kinase 2 / biosynthesis
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • G1 Phase Cell Cycle Checkpoints / drug effects*
  • Gallbladder Neoplasms / drug therapy
  • Gallbladder Neoplasms / pathology*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Lignans / pharmacology*
  • Medicine, Chinese Traditional
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Tumor Suppressor Protein p53 / antagonists & inhibitors*
  • Tumor Suppressor Protein p53 / metabolism
  • Xenograft Model Antitumor Assays
  • cdc25 Phosphatases / biosynthesis

Substances

  • Antineoplastic Agents
  • Biphenyl Compounds
  • CCND1 protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Lignans
  • Tumor Suppressor Protein p53
  • magnolol
  • Cyclin D1
  • Nitric Oxide Synthase
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • CDC25A protein, human
  • cdc25 Phosphatases