Naringenin suppresses colorectal Cancer progression by targeting the Gankyrin/PI3K /AKT/GSK-3β/β-catenin signaling

Chengxing Wang1,2, Weixing Lin1,2, Chunbo Wu3

  • 1Department of Gastrointestinal Surgery, Jiangmen Central Hospital, Jiangmen, 529000 China.

Cytotechnology
|April 14, 2026
PubMed

Insights

Naringenin, a natural compound, effectively inhibits colorectal cancer (CRC) growth and spread by targeting the Gankyrin/PI3K/AKT pathway. This study supports naringenin as a potential safe and effective therapeutic agent for CRC treatment.

Area of Science:

  • Pharmacology
  • Oncology
  • Molecular Biology

Background:

  • Colorectal cancer (CRC) is a leading global malignancy.
  • Natural products, like naringenin (NAR) from Traditional Chinese Medicine (TCM), show promise for cancer therapy due to multitarget effects and low toxicity.
  • The precise anti-CRC mechanisms of naringenin are not fully understood.

Purpose of the Study:

  • To elucidate the anti-colorectal cancer mechanisms of naringenin (NAR).
  • To investigate the role of the Gankyrin/PI3K/AKT signaling pathway in NAR's anti-cancer effects.
  • To evaluate NAR's therapeutic potential and safety in preclinical models.

Main Methods:

  • Combined network pharmacology, molecular docking, and experimental validation (in vitro and in vivo).
  • Utilized bioinformatics databases to identify NAR-CRC overlapping targets.
  • Assessed NAR's effects on CRC cell proliferation, migration, invasion, and apoptosis, and tumor growth in a xenograft model.

Main Results:

  • Network pharmacology identified AKT1 as a key target, implicating the PI3K-AKT signaling pathway.
  • Naringenin dose-dependently inhibited CRC cell proliferation, migration, and invasion, while promoting apoptosis.
  • NAR significantly suppressed tumor growth in vivo without systemic toxicity, by attenuating the Gankyrin-PI3K-AKT-GSK-3β-β-catenin axis.

Conclusions:

  • Naringenin exerts anti-CRC effects through the Gankyrin/PI3K/AKT/GSK-3β/β-catenin pathway.
  • Gankyrin plays a role in mediating naringenin's anti-cancer activity.
  • Naringenin demonstrates potential as a safe and effective therapeutic agent for colorectal cancer.

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