Piperine enhances the efficacy of TRAIL-based therapy for triple-negative breast cancer cells

Anticancer Res. 2014 Apr;34(4):1893-9.


Background/aim: Triple-negative breast cancer (TNBC) is most the aggressive type of breast cancer and is poorly responsive to endocrine therapeutics; however, one of the most attractive treatments is tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-based therapies. To identify compounds that enhance the efficacy of TRAIL-based therapies, we screened 55 compounds from natural products in combination with TRAIL in TNBC cells.

Materials and methods: Human TNBC cells, MDA-MB-468 and MDA-MB-231, and murine TNBC cells, 4T1, were used. Cell viability, apoptotic cells, and cell cycle were quantified by the WST-1 assay, annexin-V/7-amino-actinomycinD (7-AAD) staining and Propidium iodide (PI) staining, respectively. In vivo effects of piperine were evaluated in the orthotopic-inoculated 4T1-luc mouse model.

Results: After screening, we identified piperine as the most potent adjuvant at enhancing the efficacy of TRAIL-based therapies in TNBC cells in vitro and in vivo, which might be mediated through inhibition of survivin and p65 phosphorylation.

Conclusion: Piperine may enhance TRAIL-based therapeutics for TNBC.

Keywords: TRAIL; Triple-negative breast cancer; apoptosis; piperine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemistry
  • Alkaloids / pharmacology*
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Benzodioxoles / chemistry
  • Benzodioxoles / pharmacology*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Drug Synergism
  • Female
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism
  • Mice
  • Phosphorylation / drug effects
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Polyunsaturated Alkamides / chemistry
  • Polyunsaturated Alkamides / pharmacology*
  • Survivin
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology*
  • Transcription Factor RelA / metabolism
  • Triple Negative Breast Neoplasms* / metabolism
  • Triple Negative Breast Neoplasms* / pathology
  • Tumor Burden / drug effects


  • Alkaloids
  • Antineoplastic Agents
  • BIRC5 protein, human
  • Benzodioxoles
  • Inhibitor of Apoptosis Proteins
  • Piperidines
  • Polyunsaturated Alkamides
  • Survivin
  • TNF-Related Apoptosis-Inducing Ligand
  • Transcription Factor RelA
  • piperine