title: Antitumor efficacy of piperine in the treatment of human HER2-overexpressing breast cancer cells.
abstract: Piperine is a bioactive component of black pepper, Piper nigrum Linn, commonly used for daily consumption and in traditional medicine. Here, the molecular mechanisms by which piperine exerts antitumor effects in HER2-overexpressing breast cancer cells was investigated. The results showed that piperine strongly inhibited proliferation and induced apoptosis through caspase-3 activation and PARP cleavage. Furthermore, piperine inhibited HER2 gene expression at the transcriptional level. Blockade of ERK1/2 signaling by piperine significantly reduced SREBP-1 and FAS expression. Piperine strongly suppressed EGF-induced MMP-9 expression through inhibition of AP-1 and NF-κB activation by interfering with ERK1/2, p38 MAPK, and Akt signaling pathways resulting in a reduction in migration. Finally, piperine pretreatment enhanced sensitization to paclitaxel killing in HER2-overexpressing breast cancer cells. Our findings suggest that piperine may be a potential agent for the prevention and treatment of human breast cancer with HER2 overexpression.
authors.affiliation: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 305-764, South Korea.
authors.forename: Minh Truong
authors.initials: MT
authors.lastname: Do
authors.forename: Hyung Gyun
authors.initials: HG
authors.lastname: Kim
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Choi
authors.forename: Tilak
authors.initials: T
authors.lastname: Khanal
authors.forename: Bong Hwan
authors.initials: BH
authors.lastname: Park
authors.forename: Thu Phuong
authors.initials: TP
authors.lastname: Tran
authors.forename: Tae Cheon
authors.initials: TC
authors.lastname: Jeong
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D052117:Benzodioxoles / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D010880:Piperidines / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D052117:Benzodioxoles; D053148:Caspase 3; D010880:Piperidines; D010936:Plant Extracts; D053284:Polyunsaturated Alkamides; D018719:Erb-b2 Receptor Tyrosine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C508053:ERBB2 protein, human; C008922:piperine
keywords: AKT; Apoptosis; EGF; FAS; HER2; MAPKs; MMP-2/-9; MMP-9; Migration; PARP; Piperine; SREBP-1; epidermal growth factor; fatty acid synthase; human epidermal growth factor receptor 2; matrix metalloproteinase (MMP)-2/-9; mitogen-activated protein kinases; poly-ADPribose polymerase; protein kinase B; sterol regulatory element-binding protein-1