Magnolol induces apoptosis via caspase-independent pathways in non-small cell lung cancer cells

Arch Pharm Res. 2014 Apr;37(4):548-57. doi: 10.1007/s12272-013-0232-1. Epub 2013 Aug 14.

Abstract

Magnolol, a hydroxylated biphenyl agent isolated from herbal planet Magnolia officinalis, is a component of traditional Asian herbal teas. It has been reported to have anti-microbial, anti-inflammatory, and anti-cancer activity. Non-small cell lung cancer (NSCLC) cell lines (A549, H441 and H520) and normal human bronchial epithelial cells (HBECs) were used to evaluate the cytotoxic effect of magnolol. We show that magnolol inhibited cellular proliferation, increased DNA fragmentation, and decreased mitochondrial membrane potential in all NSCLC cells, but had no cytotoxic effect on HBECs. Magnolol triggered the release of pro-apoptotic proteins: Bid, Bax and cytochrome c from mitochondria, but did not activate the caspase-3, -8, and -9, suggesting that magnolol induces apoptosis of NSCLC cell lines via a caspase-independent pathway. The caspase-independent pathway is mediated through the activation of nuclear translocation of apoptosis-inducing factor, endonuclease G and cleaved poly(ADP-ribose) polymerase, which played important roles in mediating cell death. Furthermore, magnolol inhibited PI3K/AKT and ERK1/2 activity, but up-regulated p38 and JNK activity in A549 cell lines. The results of this study provided a basis for understanding and developing magnolol as a novel treatment of NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / drug effects
  • Apoptosis Regulatory Proteins / metabolism
  • Biphenyl Compounds / pharmacology*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Caspases
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA Fragmentation / drug effects
  • Drug Screening Assays, Antitumor
  • Humans
  • Lignans / pharmacology*
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Respiratory Mucosa / drug effects
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • Biphenyl Compounds
  • Lignans
  • magnolol
  • Caspases