Probiotic-derived enzyme selectively kills colon cancer cells with extremely low effective dose.

Arginine deiminase (ADI) depletes arginine—an amino acid many cancer cells cannot synthesize themselves. This study tested a recombinant ADI from the probiotic bacterium Limosilactobacillus reuteri against HCT116 colorectal cancer cells.

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Probiotic-derived enzyme selectively kills colon cancer cells with extremely low effective dose.

Probiotic-derived enzyme selectively kills colon cancer cells with extremely low effective dose.

Arginine deiminase (ADI) depletes arginine—an amino acid many cancer cells cannot synthesize themselves. This study tested a recombinant ADI from the probiotic bacterium Limosilactobacillus reuteri against HCT116 colorectal cancer cells.

LrADI achieved an IC50 of just 0.1 µg/mL—very potent—with no toxicity to normal CCD-18Co colon fibroblasts at the same concentration. Beyond killing cells, LrADI reduced clonogenic survival, suppressed cell migration, inhibited colon cancer stem cell growth (colonospheroids), and induced apoptosis through both intrinsic and extrinsic pathways.

Its probiotic origin offers potential biocompatibility advantages. The multi-faceted anti-cancer activity profile makes it an interesting early-stage candidate.

Key Findings

  • LrADI IC50 of 0.1 µg/mL in HCT116 colorectal cancer cells
  • No toxicity to normal CCD-18Co colon fibroblasts at effective concentrations
  • Suppressed clonogenic survival, cell migration, and cancer stem cell spheroid formation
  • Induced apoptosis via both intrinsic and extrinsic pathways
  • Probiotic (Limosilactobacillus reuteri) origin suggests favorable biocompatibility profile

Implications

LrADI is a promising early-stage candidate for colorectal cancer treatment, particularly valuable for its selective cancer cell toxicity. Probiotic-derived therapeutics may be more easily tolerated than synthetic agents. In vivo and clinical validation are the critical next steps.

Caveats

In vitro cell line study; abstract-only. HCT116 is one cell line—results may not generalize. In vivo pharmacokinetics and stability unknown. Arginine depletion has potential systemic effects. Significant translational gap to clinical use.

Source: Molecular biology reports — 2026-04-10

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