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Licochalcone C suppresses gastric cancer progression and enhances 5-FU chemosensitivity by targeting RAC3-mediated

Qingshui Wang1, Yiping Lu1, Yuluo Chen2

  • 1The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, College of Integrative Medicine, Fujian-Hong Kong-Macau-Taiwan Collaborative Laboratory for the Inheritance and Innovation of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China.

Phytomedicine : International Journal of Phytotherapy and Phytopharmacology
|July 31, 2026
PubMed
Abstract

Insights

Licochalcone C enhances chemotherapy for gastric cancer by targeting RAC3, improving 5-fluorouracil (5-FU) sensitivity. This natural compound inhibits key cancer pathways and reduces drug resistance, offering a promising adjuvant therapy.

Area of Science:

  • Oncology
  • Pharmacology
  • Natural Products Chemistry

Background:

  • Gastric cancer is a leading cause of cancer mortality globally.
  • Limited sensitivity to 5-fluorouracil (5-FU) hinders effective gastric cancer chemotherapy.
  • Licochalcones from licorice show anticancer potential, but Licochalcone C's role in 5-FU chemosensitivity is unknown.

Purpose of the Study:

  • To investigate Licochalcone C's antitumor effects in gastric cancer.
  • To evaluate Licochalcone C's ability to enhance 5-FU chemosensitivity.
  • To elucidate the molecular mechanisms underlying these effects.

Main Methods:

  • Utilized human gastric cancer cell lines, patient-derived organoids, clinical specimens, and a mouse xenograft model.
  • Assessed cell proliferation, colony formation, migration, invasion, and cell cycle.
  • Employed mass spectrometry, molecular docking, and Western blot analyses for target identification and mechanism elucidation.

Main Results:

  • Licochalcone C inhibited gastric cancer cell proliferation, migration, and invasion, inducing G1 arrest.
  • Significantly enhanced 5-FU sensitivity across cell lines, organoids, and xenograft models.
  • Identified direct binding of Licochalcone C to RAC3, suppressing the PI3K-AKT-mTOR pathway and downregulating P-glycoprotein.

Conclusions:

  • Licochalcone C acts as a RAC3-targeting chemosensitizer for gastric cancer.
  • Enhances 5-FU efficacy by inhibiting PI3K-AKT-mTOR signaling and P-glycoprotein.
  • Supports Licochalcone C's development as a therapeutic adjuvant for gastric cancer.
Keywords:
5-FUCell cycleGastric cancerLicochalcone CRAC3

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