Related Experiment Video

Updated: Aug 16, 2026

Bacterial Expression and Purification of Human Matrix Metalloproteinase-3 using Affinity Chromatography
07:32

Bacterial Expression and Purification of Human Matrix Metalloproteinase-3 using Affinity Chromatography

Published on: March 30, 2022

A small compound that inhibits tumor necrosis factor-alpha-induced matrix metalloproteinase-9 upregulation

Ha Young Lee1, Kyoung Sun Park, Mi-Kyoung Kim

  • 1Medical Research Center for Cancer Molecular Therapy and Department of Biochemistry, College of Medicine, Dong-A University, Busan 602-714, Republic of Korea.

Biochemical and Biophysical Research Communications
|September 6, 2005
PubMed

Insights

A novel compound, SM-7368, effectively inhibits tumor cell invasion by blocking tumor necrosis factor-alpha (TNF-alpha)-induced matrix metalloproteinase-9 (MMP-9) expression and activity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Matrix metalloproteinase-9 (MMP-9) is crucial for tumor invasion and metastasis.
  • Tumor necrosis factor-alpha (TNF-alpha) significantly regulates MMP-9 expression.
  • Targeting TNF-alpha signaling pathways is a key strategy for cancer therapy.

Purpose of the Study:

  • To identify and characterize novel synthetic compounds that inhibit TNF-alpha-induced MMP-9 expression.
  • To evaluate the efficacy of SM-7368 in blocking cancer cell invasion.
  • To elucidate the molecular mechanisms underlying SM-7368's anti-cancer activity.

Main Methods:

  • HT1080 human fibrosarcoma cell line was used for in vitro studies.
  • SM-7368's effect on TNF-alpha-induced MMP-9 upregulation was assessed at mRNA and protein levels.
  • NF-kappaB and AP-1 activity assays were performed to determine the signaling pathways affected.
  • Cell invasion assays were conducted to evaluate the functional impact of SM-7368.

Main Results:

  • SM-7368 demonstrated potent, dose-dependent inhibition of TNF-alpha-induced MMP-9 upregulation, with maximal activity at 10 microM.
  • SM-7368 suppressed both MMP-9 mRNA transcript accumulation and protein expression.
  • The compound strongly inhibited TNF-alpha-induced NF-kappaB activity, but not AP-1 activity.
  • SM-7368 significantly reduced the invasive potential of HT1080 cells in vitro.

Conclusions:

  • SM-7368 is a novel synthetic compound that effectively inhibits TNF-alpha-induced MMP-9 expression and activity.
  • SM-7368 targets the NF-kappaB signaling pathway, a key mediator of MMP-9 upregulation.
  • These findings suggest SM-7368 holds promise for developing novel chemotherapies against TNF-alpha-mediated tumor invasion and metastasis.

Related Concept Videos

Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...