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Plant seed protease inhibitors differentially affect innate immunity in a tumor microenvironment to control

J M Laparra1, C M Haros

  • 1Molecular Immunonutrition Group, Madrid Institute for Advanced Studies in Food (IMDEA-Food), Ctra. de Canto Blanco n° 8, 28049 Madrid, Spain. moises.laparra@imdea.org.

Food & Function
|July 2, 2019
PubMed

Insights

Serine-type protease inhibitors (STPIs) from quinoa and chia seeds show promise for controlling liver cancer (HCC). These plant-derived compounds modulate immune responses and macrophage polarization, offering a potential therapeutic strategy.

Area of Science:

  • Biochemistry
  • Immunology
  • Plant Science

Background:

  • Understanding foodstuff tolerance is crucial for metabolic diseases.
  • Serine-type protease inhibitors (STPIs) play roles in biological processes.
  • Hepatocellular carcinoma (HCC) requires novel therapeutic approaches.

Purpose of the Study:

  • To comparatively analyze STPIs from *Chenopodium quinoa*, *Salvia hispanica* L., *Avena sativa*, and *Triticum durum*.
  • To evaluate the in vivo effects of these STPIs on a hepatocarcinoma (HCC) model.
  • To explore the potential of STPIs from *C. quinoa* and *S. hispanica* in controlling HCC aggressiveness.

Main Methods:

  • Comparative structural and functional analysis of STPIs.
  • Protease inhibitory capacity assays.
  • High-Performance Liquid Chromatography-Reversed Phase-Electrospray Ionization (HPLC-RP-ESI) analysis.
  • In vivo study using an HCC model, assessing F4/80+ cells, CD36 and Toll-like receptor (TLR)-4 mRNA expression, and inflammatory mediator production.

Main Results:

  • STPIs exhibited varying protease inhibitory capacities, with *C. quinoa* and *S. hispanica* showing lower capacity than *A. sativa* and *T. durum*.
  • *C. quinoa* and *S. hispanica* STPIs formed heterologous complexes, while *A. sativa* had homologous complexes; *T. durum* yielded diverse subunits.
  • STPIs from *S. hispanica* positively influenced the HCC model by increasing F4/80+ cells and normalizing CD36 and TLR-4 expression.
  • STPIs from *C. quinoa* and *S. hispanica* maintained M1 macrophage polarization and did not impair key inflammatory mediators.

Conclusions:

  • STPIs from *C. quinoa* and *S. hispanica* possess structural and functional characteristics beneficial for managing HCC.
  • These specific plant-derived STPIs demonstrate immunomodulatory effects relevant to antitumoral responses.
  • The findings suggest potential applications of *C. quinoa* and *S. hispanica* STPIs as therapeutic agents against HCC aggressiveness.

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