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.
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.
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