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Itraconazole exerts anti-liver cancer potential through the Wnt, PI3K/AKT/mTOR, and ROS pathways

Wenping Wang1, XiaoXv Dong1, Yi Liu1

  • 1School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100102, China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|September 17, 2020
PubMed

Insights

Itraconazole, an antifungal drug, effectively inhibits liver cancer cell growth and induces apoptosis. This study explores its anti-cancer mechanisms, suggesting potential as a new liver cancer treatment.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Hepatocellular carcinoma (HCC) presents high mortality, necessitating novel therapeutic agents.
  • Itraconazole, an antifungal, exhibits anti-tumor properties, but its specific efficacy against HCC remains uninvestigated.

Purpose of the Study:

  • To evaluate the anti-liver cancer effects of itraconazole.
  • To elucidate the underlying anti-cancer mechanisms of itraconazole in HCC.

Main Methods:

  • MTT assay for proliferation, flow cytometry for apoptosis, cell cycle, ROS, and MMP.
  • DAPI staining for nuclear morphology, LDH assay for cell damage, and Western blotting for signaling pathways.

Main Results:

  • Itraconazole significantly inhibited HepG2 and Bel-7405 cell proliferation.
  • It induced apoptosis, increased ROS, arrested cell cycle, and reduced MMP in HCC cells.
  • Mechanistically, itraconazole impacted Hh, Wnt/catenin, AKT/mTOR/S6K, ROS, and death receptor pathways.

Conclusions:

  • Itraconazole demonstrates significant anti-liver cancer activity.
  • It holds potential as a novel therapeutic drug for clinical application in HCC treatment.
Keywords:
HepG2 cellsItraconazolePI3K/AKT/mTOR pathwayWnt/β-catenin pathway

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