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Inhibitory effects of 4-hydroperoxy-2-decenoic acid ethyl ester on phorbol ester- and TGF-β1-induced MMPs expression

Tetsuro Kamiya1, Miho Tanaka1, Hirokazu Hara1

  • 1Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan.

Free Radical Research
|October 3, 2019
PubMed

Insights

4-Hydroperoxy-2-decenoic acid ethyl ester (HPO-DAEE) inhibits matrix metalloproteinases (MMPs) and reduces cancer cell migration. This compound shows potential for suppressing tumor progression and metastasis by targeting MMPs.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Matrix metalloproteinases (MMPs) are crucial for tumor progression and metastasis by degrading extracellular matrix.
  • MMP2 and MMP9 are key players in tumor microenvironment formation.
  • 4-Hydroperoxy-2-decenoic acid ethyl ester (HPO-DAEE) induces apoptosis in lung cancer cells via ER stress, but its effect on tumor progression is unknown.

Purpose of the Study:

  • To investigate the effects of HPO-DAEE on tumor progression, specifically its impact on MMPs and cancer cell migration.
  • To determine if HPO-DAEE can suppress MMP activation and related cellular processes.

Main Methods:

  • Assessing MMP activation in THP-1 cells pre-treated with HPO-DAEE and stimulated with TPA.
  • Measuring haem oxygenase-1 expression and reactive oxygen species (ROS) levels.
  • Evaluating the effect of HPO-DAEE on PC3 prostate cancer cell migration triggered by TGF-β1.
  • Analyzing MMP expression and activity in response to HPO-DAEE treatment.

Main Results:

  • HPO-DAEE pre-treatment significantly suppressed TPA-induced MMP activation in THP-1 cells.
  • HPO-DAEE enhanced haem oxygenase-1 expression and reduced intracellular ROS accumulation.
  • HPO-DAEE inhibited TGF-β1-induced migration of PC3 prostate cancer cells.
  • These migratory effects were associated with suppressed MMP expression and activity.

Conclusions:

  • HPO-DAEE demonstrates inhibitory effects on tumor progression.
  • Suppression of MMP expression and activity is a key mechanism by which HPO-DAEE exerts its anti-tumor effects.
  • HPO-DAEE holds potential as a therapeutic agent for inhibiting cancer metastasis.
Keywords:
HO-1HPO-DAEEMMPsROS

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