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Updated: Jan 26, 2026

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Novel screening system revealed that intracellular cholesterol trafficking can be a good target for colon cancer

Shingo Miyamoto1,2, Takumi Narita1, Masami Komiya1

  • 1Division of Prevention, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Scientific Reports
|April 19, 2019
PubMed

Insights

This study identified 8 potential colon cancer chemopreventive drugs by screening 1280 compounds. Itraconazole, an antifungal, significantly reduced intestinal polyps in mice by modulating key cellular pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Conventional cancer prevention often targets cell proliferation and apoptosis, neglecting normal cell protection.
  • Malignant transformation involves critical transcriptional activities of TCF/LEF, NF-κB, and NRF2.
  • Developing novel chemopreventive strategies is crucial for colorectal cancer (CRC).

Purpose of the Study:

  • To identify candidate colon cancer chemopreventive drugs.
  • To screen for compounds modulating TCF/LEF, NF-κB, and NRF2 transcriptional activity.
  • To evaluate drug efficacy in a preclinical model.

Main Methods:

  • Screening a library of 1280 approved drugs.
  • Assessing compounds for decreased TCF/LEF and NF-κB activity, and increased NRF2 activity.
  • Utilizing the Min mouse model to test candidate itraconazole efficacy.

Main Results:

  • Eight compounds were identified as potential CRC chemopreventive agents.
  • Itraconazole, an antifungal drug, significantly suppressed intestinal polyp formation in the Min mouse model.
  • Itraconazole's effects may involve inhibiting intracellular cholesterol trafficking.

Conclusions:

  • This study presents a novel approach for identifying chemopreventive agents using integrated transcriptional activity criteria.
  • Itraconazole shows promise as a chemopreventive drug for colorectal cancer.
  • Targeting TCF/LEF, NF-κB, and NRF2 pathways offers a new avenue for cancer prevention research.

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