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Updated: Sep 21, 2025

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GPR108 is required for gambogic acid inhibiting NF-κB signaling in cancer

Song Lyu1, Xue Zhang1, Zhenzhen Tu2

  • 1Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Pharmacological Research
|June 6, 2022
PubMed

Insights

This study identifies G protein-coupled receptor 108 (GPR108) as a novel cancer target. Gambogic acid selectively inhibits GPR108, demonstrating potent anti-cancer activity by blocking NF-κB signaling.

Area of Science:

  • Oncology
  • Immunology
  • Pharmacology

Background:

  • G protein-coupled receptors (GPCRs) are crucial drug targets, but their role in cancer is underexplored.
  • GPR108, a GPCR involved in innate immunity, presents an underappreciated therapeutic target in oncology.

Purpose of the Study:

  • To investigate GPR108 as a potential anti-cancer target.
  • To identify and characterize small molecule inhibitors of GPR108 for cancer therapy.

Main Methods:

  • GPR108 knockout and depletion in various cancer models.
  • Analysis of TNFα/NF-κB signaling pathway.
  • Identification and characterization of gambogic acid (GA) as a GPR108 inhibitor.
  • In vitro and in vivo anti-cancer activity assays.

Main Results:

  • GPR108 depletion significantly inhibited cancer cell survival.
  • GPR108 knockout abolished TNFα activation of NF-κB signaling.
  • Gambogic acid selectively targets GPR108, promoting its degradation.
  • GA's anti-cancer effects were dependent on GPR108 expression and its inhibition of NF-κB signaling.

Conclusions:

  • GPR108 is a promising therapeutic target for cancer treatment.
  • Gambogic acid is a novel, selective small molecule inhibitor of GPR108 with potential for cancer therapy.
Keywords:
CancerG protein-coupled receptorsGPR108Gambogic acidNF-κB

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