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Anti-Cancer Roles of Probiotic-Derived P8 Protein in Colorectal Cancer Cell Line DLD-1.

Byung Chull An1, Jun Young Ahn1, Daebeom Kwon1

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International Journal of Molecular Sciences
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A novel protein from probiotics, P8, halts colorectal cancer (CRC) growth by disrupting cell cycle regulation and Wnt signaling pathways. This discovery offers a new therapeutic avenue for CRC treatment.

Keywords:
KCTC 12202BPLactobacillus rhamnosusP8anti-cancer activityanti-cancer target proteinbiotherapeuticprobioticsprotein-protein interaction

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Area of Science:

  • Molecular Biology
  • Cancer Research
  • Microbiology

Background:

  • Colorectal cancer (CRC) remains a significant health challenge.
  • Probiotics-derived compounds show potential in cancer therapy.
  • The precise mechanisms of P8's anti-cancer effects are not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which P8 suppresses colorectal cancer (CRC) cell growth.
  • To identify proteins involved in P8's cellular uptake and its downstream targets.
  • To investigate P8's impact on cell cycle regulation and Wnt signaling in CRC.

Main Methods:

  • Pull-down assays using P8 as bait to identify interacting proteins in DLD-1 cell lysates.
  • Analysis of P8's localization and interactions within the cytosol and nucleus.
  • Assessment of P8's effect on GSK3β activity, β-catenin degradation, and gene transcription.

Main Results:

  • Identified KPNA3 and GSK3β as P8-interacting proteins.
  • P8 prevents GSK3β inactivation in the cytosol, leading to β-catenin degradation.
  • P8 translocates to the nucleus via KPNA3, where it dysregulates GSK3β gene transcription.

Conclusions:

  • P8 suppresses CRC growth by inhibiting GSK3β and down-regulating Wnt signaling.
  • P8 induces cell cycle arrest in CRC cells, even under Wnt-activated conditions.
  • P8 represents a promising therapeutic agent for colorectal cancer.