Piperlongumine‑loaded nanoparticles inhibit the growth, migration and invasion and epithelial‑to‑mesenchymal transition of triple‑negative breast cancer cells

Abstract

Metastasis and disease relapse are the major causes of morbidity and mortality among patients with triple‑negative breast cancer (TNBC). Novel therapeutics that interfere with the process of metastasis, including epithelial‑to‑mesenchymal transition (EMT), are thus urgently required. Piperlongumine (PL) is a component of the fruits of the long pepper plant ( Piper longum), which are used as a spice and in traditional medicine. The present study compared the anti‑metastatic potential of free PL and PL‑loaded nanoparticles (PL‑NPs) in TNBC cells. PL was loaded into biodegradable methoxy poly(ethylene glycol)‑poly‑(lactide‑­co‑glycolic) acid copolymer NPs by thin‑film hydration. The effects of free PL and PL‑NPs on TNBC cells were compared using colorimetric MTT assays for cell growth/viability, Transwell assays for migration/invasiveness, and western blot analysis and reverse transcription‑quantitative polymerase chain reaction for expression of EMT‑associated proteins and DNA methyltransferase‑1. PL‑NPs reduced MDA‑MB‑231, MDA‑MB‑468, and BT‑549 TNBC cell growth/viability to the same extent as free PL. Treatment of the MDA‑MB‑231 cells with both PL‑NPs and free PL inhibited migration/invasiveness, reduced the expression of matrix metalloproteinase 2 and EMT‑promoting Slug, ZEB1, N‑cadherin, β‑catenin and Smad3, promoted E‑cadherin and anti‑metastatic n‑Myc downstream regulated gene 1 expression, and inhibited the expression of oncogenic DNA methyltransferase‑1. On the whole, the present study demonstrated that PL‑NPs inhibited the metastasis‑promoting activities of TNBC cells to the same extent as free PL, highlighting the feasibility of employing NPs for the delivery of PL to prevent or reduce TNBC metastasis.