title: Piperine inhibits the growth and motility of triple-negative breast cancer cells.
abstract: Piperine, an alkaloid from black pepper, is reported to have anticancer activities. In this study, we investigated the effect of piperine on the growth and motility of triple-negative breast cancer (TNBC) cells. Piperine inhibited the in vitro growth of TNBC cells, as well as hormone-dependent breast cancer cells, without affecting normal mammary epithelial cell growth. Exposure to piperine decreased the percentage of TNBC cells in the G2 phase of the cell cycle. In addition, G1- and G2-associated protein expression was decreased and p21(Waf1/Cip1) expression was increased in piperine-treated TNBC cells. Piperine also inhibited survival-promoting Akt activation in TNBC cells and caused caspase-dependent apoptosis via the mitochondrial pathway. Interestingly, combined treatment with piperine and γ radiation was more cytotoxic for TNBC cells than γ radiation alone. The in vitro migration of piperine-treated TNBC cells was impaired and expression of matrix metalloproteinase-2 and -9 mRNA was decreased, suggesting an antimetastatic effect by piperine. Finally, intratumoral administration of piperine inhibited the growth of TNBC xenografts in immune-deficient mice. Taken together, these findings suggest that piperine may be useful in the treatment of TNBC.
authors.affiliation: Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4R2.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Greenshields
authors.affiliation: Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4R2.
authors.forename: Carolyn D
authors.initials: CD
authors.lastname: Doucette
authors.affiliation: Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4R2.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Sutton
authors.affiliation: Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4R2.
authors.forename: Laurence
authors.initials: L
authors.lastname: Madera
authors.affiliation: Department of Biology, Saint Mary's University, Halifax, Nova Scotia, Canada B3H 3C3.
authors.forename: Henry
authors.initials: H
authors.lastname: Annan
authors.affiliation: Department of Surgery, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4R2.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Yaffe
authors.affiliation: Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4R2.
authors.forename: Allison F
authors.initials: AF
authors.lastname: Knickle
authors.affiliation: Department of Biology, Saint Mary's University, Halifax, Nova Scotia, Canada B3H 3C3.
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4R2; Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4R2; Department of Biology, Saint Mary's University, Halifax, Nova Scotia, Canada B3H 3C3. Electronic address: d.w.hoskin@dal.ca.
authors.forename: David W
authors.initials: DW
authors.lastname: Hoskin
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D052117:Benzodioxoles / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010880:Piperidines / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D015398:Signal Transduction; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000470:Alkaloids; D052117:Benzodioxoles; D010880:Piperidines; D053284:Polyunsaturated Alkamides; C008922:piperine
keywords: Apoptosis; Breast cancer; Metastasis; Piperine; Xenograft