title: Piperine enhances the efficacy of TRAIL-based therapy for triple-negative breast cancer cells.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Piperine may enhance TRAIL-based therapeutics for TNBC.
authors.affiliation: Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. byosei@inm.u-toyama.ac.jp.
authors.forename: Sherif
authors.initials: S
authors.lastname: Abdelhamed
authors.forename: Satoru
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Alaa
authors.initials: A
authors.lastname: Refaat
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ogura
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Suresh
authors.initials: S
authors.lastname: Awale
authors.forename: Ikuo
authors.initials: I
authors.lastname: Saiki
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D052117:Benzodioxoles / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004357:Drug Synergism; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000737:chemistry / Q000494:pharmacology*; D000077022:Survivin; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D052117:Benzodioxoles; D051034:Inhibitor of Apoptosis Proteins; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D000077022:Survivin; D053221:TNF-Related Apoptosis-Inducing Ligand; D051996:Transcription Factor RelA; C008922:piperine
keywords: TRAIL; Triple-negative breast cancer; apoptosis; piperine