[New compound NL-608 (a nutlin analog) induces apoptosis in human breast cancer MCF-7 cells]

Zhonghua Zhong Liu Za Zhi. 2012 Feb;34(2):100-3. doi: 10.3760/cma.j.issn.0253-3766.2012.02.005.
[Article in Chinese]

Abstract

Objective: To observe the effect of NL-608 (a nutlin analog) on apoptosis induction in human breast cancer MCF-7 cells in vitro, and investigate the relevant molecular mechanism.

Methods: The effect of NL-608 on proliferation of MCF-7 cells was determined by MTT assay. The apoptosis in MCF-7 cells was determined by flow cytometry with annexin V-FITC and PI. The activity of caspase 3, caspase 8 and caspase 9 was determined with caspase activity assay kit and Western blot, and the proteins of Fas and FasL were determined by Western blot.

Results: NL-608 showed a dose-dependent inhibitory effect on the proliferation of MCF-7 cells. It induced apoptosis in MCF-7 cells in a dose-dependent manner. The activity of caspase 3 and caspase 8 in MCF-7 cells was increased with the increasing concentration of NL-608, but caspase 9 had no changes. The proteins of Fas and FasL were increased in a dose-dependent manner.

Conclusion: NL-608 induces apoptosis in MCF-7 cells in vitro through inducing caspase 3 activity and death receptor-mediated signal pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism*
  • Caspase 8 / metabolism
  • Caspase 9 / metabolism
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Fas Ligand Protein / metabolism
  • Humans
  • Imidazoles / pharmacology*
  • MCF-7 Cells
  • Piperazines / pharmacology*
  • fas Receptor / metabolism

Substances

  • Antineoplastic Agents
  • FAS protein, human
  • FASLG protein, human
  • Fas Ligand Protein
  • Imidazoles
  • NL-608
  • Piperazines
  • fas Receptor
  • nutlin 3
  • CASP3 protein, human
  • CASP8 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 8
  • Caspase 9