Induction of laryngeal cancer cell death by Ent-11-hydroxy-15-oxo-kaur-16-en-19-oic acid

Head Neck. 2010 Nov;32(11):1506-18. doi: 10.1002/hed.21357.

Abstract

Background: Ent-11-hydroxy-15-oxo-kaur-16-en-19-oic acid (5F) is known to exhibit antitumor activity, but its mechanism is not completely understood. 5F has not been tested in laryngeal cancer.

Methods: Two laryngeal cancer cell lines were treated with 5F. Cell death was analyzed by MTT [3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyltetrazolium bromide] and Annexin V assay. Nuclear factor kappa beta (NF-κB)- and apoptosis-related molecules were examined.

Results: 5F induced laryngeal cancer cell death in a dose-dependent manner. The Annexin V assay and the measurement of cleavage of procaspase-3 and poly(ADP-ribose) polymerase demonstrated that the 5F-induced cell death was mainly apoptotic. 5F slightly reduced the basal level of NF-κB, but significantly suppressed the inducible NF-κB by reducing its transcriptional activity, protecting its inhibitory subunit IκBα from degradation, and suppressing its level in the nucleus. 5F also inhibited pro-proliferative and anti-apoptotic molecules but promoted pro-apoptotic Bax.

Conclusions: 5F induces apoptosis of laryngeal cancer cells by inhibiting NF-κB activation/induction, suppressing pro-proliferative and anti-apoptotic molecules, and promoting pro-apoptotic Bax.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Blotting, Western
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclin D1 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Drugs, Chinese Herbal / pharmacology*
  • ErbB Receptors / metabolism
  • Humans
  • I-kappa B Kinase / drug effects
  • Inhibitor of Apoptosis Proteins
  • Laryngeal Neoplasms / pathology*
  • Microtubule-Associated Proteins / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Poly(ADP-ribose) Polymerases / metabolism
  • Survivin
  • Transcription, Genetic / drug effects
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Up-Regulation / drug effects
  • bcl-2-Associated X Protein / metabolism

Substances

  • 11-hydroxy-15-oxokaur-16-en-19-olic acid
  • BAX protein, human
  • BIRC5 protein, human
  • CCND1 protein, human
  • Diterpenes
  • Drugs, Chinese Herbal
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • NF-kappa B
  • Survivin
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • Cyclin D1
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Poly(ADP-ribose) Polymerases
  • EGFR protein, human
  • ErbB Receptors
  • I-kappa B Kinase
  • Caspase 3