Anti-tumour activity of longikaurin A (LK-A), a novel natural diterpenoid, in nasopharyngeal carcinoma

J Transl Med. 2013 Aug 28:11:200. doi: 10.1186/1479-5876-11-200.

Abstract

Background: Longikaurin A is a natural ent-kaurene diterpenoid isolated from Isodon genus. The ent-kaurene diterpenoids isolated from medicinal plants have been shown to have anti-disease effects. The present study was designed to examine the anti-tumour effects of longikaurin A (LK-A) in nasopharyngeal carcinoma in vitro and in vivo.

Methods: Apoptosis and cell cycle arrest were determined by flow cytometry analysis of the cells treated with Longikaurin A. The proteins of apoptosis signaling pathway were detected by western blotting analysis. Finally, we examined whether LK-A exhibits anti-tumour activity in xenograft models.

Results: Longikaurin A inhibited the cell growth by inducing apoptosis and cell cycle arrest. At low concentrations, longikaurin A induced S phase arrest and at higher concentrations, longikaurin A induced caspase-dependent apoptosis by regulating apoptotic molecules. Finally, longikaurin A significantly inhibited the tumour growth of CNE2 xenografts in vivo and showed no obvious effect on the body weights of the mice.

Conclusion: Our results suggest that Longikaurin A exhibited anti-tumour activity in nasopharyngeal carcinoma in vitro and in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / metabolism
  • Carcinoma
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Diterpenes, Kaurane / chemistry
  • Diterpenes, Kaurane / pharmacology
  • Diterpenes, Kaurane / therapeutic use*
  • Mice
  • Mice, Nude
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / drug therapy*
  • Nasopharyngeal Neoplasms / enzymology
  • Nasopharyngeal Neoplasms / pathology
  • Poly(ADP-ribose) Polymerases / metabolism
  • S Phase / drug effects
  • Signal Transduction / drug effects
  • Tumor Stem Cell Assay
  • Up-Regulation / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Amino Acid Chloromethyl Ketones
  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • Diterpenes, Kaurane
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • longikaurin A
  • Poly(ADP-ribose) Polymerases
  • Caspase 3
  • Caspase 9