Inhibition of human tumor cell migration by a rice-derived chimeric cysteine protease inhibitor

An Acad Bras Cienc. 2024 Dec 13;96(suppl 3):e20240778. doi: 10.1590/0001-3765202420240778. eCollection 2024.

Abstract

The cystatin superfamily includes proteins crucial for inhibiting cysteine proteases, enzymes involved in many biological processes. In plants, cystatins regulate seed germination, development, and pathogen defense. In humans, inhibiting legumain-type cysteine proteases offers a promising cancer treatment strategy, as this enzyme's expression often rises during tumor progression. We evaluated a novel rice-derived chimeric legumain inhibitor using in silico and in vitro methods. Computational simulations confirmed the inhibitor's stability and nanomolar affinity for legumain's active site. Post-expression and purification assays determined its kinetics and demonstrated its efficacy in reducing HT29 tumor cell migration and viability. Our findings suggest the chimeric Oryzacystatin I mutant with SNSL motifs is a promising candidate for cancer drug development.

MeSH terms

  • Cell Movement* / drug effects
  • Cystatins / genetics
  • Cystatins / pharmacology
  • Cysteine Endopeptidases* / genetics
  • Cysteine Endopeptidases* / metabolism
  • Cysteine Proteinase Inhibitors* / pharmacology
  • HT29 Cells
  • Humans
  • Oryza* / genetics

Substances

  • Cysteine Proteinase Inhibitors
  • Cysteine Endopeptidases
  • asparaginylendopeptidase
  • Cystatins