Salicylate •Phenanthroline copper (II) complex induces apoptosis in triple-negative breast cancer cells

Oncotarget. 2017 May 2;8(18):29823-29832. doi: 10.18632/oncotarget.16161.

Abstract

In this study, we investigated anti-tumor activity and associated molecular mechanism of action of Salicylate ●Phenanthroline Copper (II) Complex in triple-negative breast cancer. Salicylate ●Phenanthroline Copper (II) Complex inhibited the growth of four breast cancer cell lines (MCF-7, T47D, MDA-MB-231 and BT-20) and induced apoptosis in a concentration-dependent manner. The effect was more profound in MDA-MB-231 and BT-20 triple-negative breast cancer cell lines. Western blot showed that the expression of the apoptosis-related protein Bcl-2, Bcl-xl and survivin was significantly reduced in MDA-MB-231 after treatment with Salicylate ●Phenanthroline Copper (II) Complex. In vivo, Salicylate ●Phenanthroline Copper (II) Complex administration significantly attenuated tumor growth of MDA-MB-231 xenografts, and the expression levels of Bcl-2, Bcl-xL and survivin were reduced as measured by immunohistochemical staining. These data suggest that Salicylate ●Phenanthroline Copper (II) Complex is a promising novel therapeutic drug for triple-negative breast cancer and warrants further study.

Keywords: Cu(sal)(phen); TNBC; anti-apoptotic protein; apoptosis; cell growth.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Biomarkers
  • Cell Line, Tumor
  • Disease Models, Animal
  • Female
  • Humans
  • Mice
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Phenanthrolines / chemistry
  • Phenanthrolines / pharmacology*
  • Salicylates / chemistry
  • Salicylates / pharmacology*
  • Triple Negative Breast Neoplasms / drug therapy
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Biomarkers
  • Organometallic Compounds
  • Phenanthrolines
  • Salicylates
  • copper salicylate complex
  • 1,10-phenanthroline