The Natural Alkaloid Piperlongumine Inhibits Metastatic Activity and Epithelial-to-Mesenchymal Transition of Triple-Negative Mammary Carcinoma Cells. (31st December 2021)

• Record Type: Journal Article
• Authors: Delaney, Leanne M.; Farias, Nathan; Ghassemi Rad, Javad; Fernando, Wasundara; Annan, Henry; Hoskin, David W.
• Is Part Of: Nutrition and cancer. Volume 73:Number 11/12(2021)
• Page Start: 2397
• Page End: 2410
• Publication Date: 2021-12-31
• Subjects: Cancer -- Periodicals; Nutrition -- Periodicals; Cancer; Nutrition; Periodicals; 616.9940654
• DOI: 10.1080/01635581.2020.1825755
• Languages: English
• ISSNs: 0163-5581

Abstract

Abstract: In this study, we determined the effect of low dose piperlongumine on the motility/invasive capacity and epithelial-to-mesenchymal transition (EMT) of MDA-MB-231 triple-negative breast cancer (TNBC) cells and the metastasis of 4T1 mouse mammary carcinoma cells. MTT assays measured the effect of piperlongumine on TNBC cell growth. Motility/invasiveness were determined by gap closure/transwell assays. Western blotting assessed ZEB1, Slug, and matrix metalloproteinase (MMP) 9 expression. Interleukin (IL) 6 was detected by ELISA. MMP2, E-cadherin, and miR-200c expression was determined by real-time quantitative polymerase chain reaction. Reactive oxygen species (ROS) were measured by flow cytometry. The orthotopic 4T1 mouse model of breast cancer was used to examine metastasis. Piperlongumine-treated MDA-MB-231 cells showed reduced motility/invasiveness, decreased MMP2 and MMP9 expression, increased miR-200c expression, reduced IL-6 synthesis, decreased expression of ZEB1 and Slug, increased E-cadherin expression, and epithelial-like morphology. Piperlongumine also inhibited transforming growth factor β-induced ZEB1 and Slug expression. ROS accumulated in piperlongumine-treated cells, while changes in metastasis-associated gene expression were ablated by exogenous glutathione. Metastasis of 4T1 cells to the lungs of BALB/c mice was dramatically reduced in piperlongumine-treated animals. These findings reveal a previously unknown capacity of low dose piperlongumine to interfere with TNBC metastasis via an oxidative stress-dependent mechanism.