Triptolide inhibits matrix metalloproteinase-9 expression and invasion of breast cancer cells through the inhibition of NF-κB and AP-1 signaling pathways

Abstract

Triptolide is a diterpenoid epoxide that is endogenously produced by the thunder god vine, Tripterygium wilfordii Hook F. Triptolide has demonstrated a variety of biological activities, including anticancer activities, in previous studies. Invasion and metastasis are the leading causes of mortality for patients with breast cancer, and the increased expression of matrix metalloproteinase-9 (MMP-9) has been shown to be associated with breast cancer invasion. Therefore, the aim of the present study was to investigate the effect of triptolide on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced cell invasion and MMP-9 expression in breast cancer cells. The expression of signal molecules was examined by western blotting, zymography and quantitative polymerase chain reaction; an electrophoretic mobility gel shift assay was also used, and cell invasiveness was measured by an in vitro Matrigel invasion assay. The MCF-7 human breast cancer cell line was treated with triptolide at the highest concentrations at which no marked cytotoxicity was evident. The results demonstrated that triptolide decreased the expression of MMP-9 through inhibition of the TPA-induced phosphorylation of extracellular signal-regulated kinase (ERK) and the downregulation of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) activity. In addition, a Transwell assay revealed that triptolide reduced the ability of MCF-7 cells to invade Matrigel. These data demonstrate that the anti-invasive effect of triptolide is associated with the inhibition of ERK signaling and NF-κB and AP-1 activation, and suggest that triptolide may be a promising drug for breast cancer.

CDDO, a PPAR‑γ ligand, inhibits TPA‑induced cell migration and invasion through a PPAR‑γ‑independent mechanism

“…MMP-9 is an important molecule that plays a major role in cancer growth and metastasis primarily via degradation of the ECM, which could result in cancer cell migration ( 11 , 12 ). Elevated MMP-9 expression is key in the invasive process of numerous cancers, especially breast cancers ( 13 ). The induction of MMP-9 is affected by many factors, such as cytokines, growth factors, and certain oncogenes.…”

Modulation of TLR/NF-κB/NLRP Signaling by Bioactive Phytocompounds: A Promising Strategy to Augment Cancer Chemotherapy and Immunotherapy

“…Triptolide is a well-known diterpenoid that blocks the NF-kB survival pathways and activates ERK1/2 and p38a in PC3 cancer cells (221). Additionally, triptolide decreased the expression of MMP-9, AP-1, and NF-kB signaling pathways in MCF-7 cells (222) and attenuated the angiogenesis and invasion of thyroid (223)(224)(225)(226). Ursolic acid (Figure 5) exerts anti-inflammatory activity via suppression of the TLR4-MyD88 pathway and decreased production of inflammatory factors, including IL-1b, TNF-a, and IL-6 in abelson murine leukemia macrophage (RAW 264.7) cells (227).…”

Genetic Interference of FGFR3 Impedes Invasion of Upper Tract Urothelial Carcinoma Cells by Alleviating RAS/MAPK Signal Activity

“…Meanwhile, EMT induction with the concurrent degradation of the extracellular matrix (ECM), which facilitates tumor metastasis, is essential for the migration and invasion of cancer cells [ 9 , 10 , 11 , 12 , 13 , 14 ]. In this regard, matrix metalloproteinases (MMPs), including MMP9, are key enzymes for ECM degradation [ 15 ], while intratumoral MMP9 expression is positively correlated with the aggressiveness of many cancers [ 14 , 15 , 16 , 17 , 18 ]. In terms of signaling, mitogen-activated protein kinase (MAPK)-mediated signaling mechanistically contributes to EMT induction and MMP9 activation [ 15 , 19 ].…”

“…In this regard, matrix metalloproteinases (MMPs), including MMP9, are key enzymes for ECM degradation [ 15 ], while intratumoral MMP9 expression is positively correlated with the aggressiveness of many cancers [ 14 , 15 , 16 , 17 , 18 ]. In terms of signaling, mitogen-activated protein kinase (MAPK)-mediated signaling mechanistically contributes to EMT induction and MMP9 activation [ 15 , 19 ]. Indeed, blockades in the EMT process and MMP activation have been considered plausible therapeutic targets for tumor treatment [ 14 , 16 ].…”