Ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid induces apoptosis and cell cycle arrest in CNE-2Z nasopharyngeal carcinoma cells

Oncol Rep. 2013 Jun;29(6):2101-8. doi: 10.3892/or.2013.2375. Epub 2013 Apr 3.

Abstract

Ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F), a compound isolated from Pteris semipinnata L. (PsL), inhibits cell proliferation and induces cell apoptosis in several cancer lines. We found that 5F induced apoptosis and G2 phase cell cycle arrest in the CNE-2Z nasopharyngeal carcinoma (NPC) cells, accompanied by a decrease of NF-κB expression. 5F suppressed the viability of CNE-2Z cells in a time- and dose-dependent manner. 5F induced G2/M phase cell cycle arrest, but did not induce p21. Further analysis revealed that CNE-2Z cells harbored two p53 mutations. 5F treatment resulted in mitochondrial apoptosis, associated with increased Bax/Bcl-2 ratio, upregulation of cytochrome c in the cytosol, decreased NF-κB-p65 and increased IκB. Of note, 5F significantly sensitized CNE-2Z cells to cisplatin. 5F did not increase ROS, but reduced ROS production alone or in combination with cisplatin. Our data suggest that 5F is a potential anti-NPC drug for the development of single agent therapy and therapy in combination with cisplatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Base Sequence
  • Carcinoma
  • Cell Line, Tumor / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cisplatin / pharmacology
  • DNA Mutational Analysis
  • Diterpenes / pharmacology*
  • Drug Synergism
  • G2 Phase Cell Cycle Checkpoints / drug effects*
  • Humans
  • I-kappa B Proteins / genetics
  • I-kappa B Proteins / metabolism
  • Molecular Sequence Data
  • NF-KappaB Inhibitor alpha
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / drug therapy*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Sequence Deletion
  • Transcription Factor RelA / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Up-Regulation

Substances

  • 11-hydroxy-15-oxokaur-16-en-19-olic acid
  • Antineoplastic Agents, Phytogenic
  • Diterpenes
  • I-kappa B Proteins
  • NFKBIA protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • RELA protein, human
  • Reactive Oxygen Species
  • TP53 protein, human
  • Transcription Factor RelA
  • Tumor Suppressor Protein p53
  • NF-KappaB Inhibitor alpha
  • Cisplatin