Quercetin induces immunogenic cell death against gastric cancer by targeting NR3C1

Ting Liu1, Ying Wang2, Min Peng3

  • 1Shandong University of Traditional Chinese Medicine, Jinan, 250013, Shandong, PR China; Department of Traditional Chinese Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, PR China; Medical College, Qilu Institute of Technology, Jinan, 250200, Shandong, PR China.

Insights

Quercetin, a natural compound, effectively combats gastric cancer by targeting NR3C1. This flavonoid reduces cancer cell growth and promotes cell death, offering a promising therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Gastric cancer presents significant global health challenges with limited therapeutic avenues.
  • Quercetin, a natural flavonoid, demonstrates anticancer properties, yet its specific mechanisms and molecular targets in gastric cancer require elucidation.
  • Understanding Quercetin's action is crucial for developing novel gastric cancer treatments.

Purpose of the Study:

  • To investigate the impact of Quercetin on gastric cancer cells.
  • To identify and validate nuclear receptor subfamily 3 group C member 1 (NR3C1) as a molecular target of Quercetin in gastric cancer.
  • To assess Quercetin's effects on cell viability, proliferation, apoptosis, endoplasmic reticulum (ER) stress, and immunogenic cell death (ICD).

Main Methods:

  • Treatment of AGS and MKN45 gastric cancer cells with Quercetin.
  • Assessment of cell viability, proliferation, apoptosis, ER stress, and ICD using standard assays.
  • Identification of Quercetin's potential targets using PharmMapper and validation of NR3C1's role through overexpression studies.
  • In vivo evaluation using a subcutaneous mouse tumor model and Western blot analysis.

Main Results:

  • Quercetin significantly inhibited gastric cancer cell viability and proliferation while inducing apoptosis, ER stress, and ICD.
  • NR3C1 was identified as a key molecular target of Quercetin, mediating its anticancer effects.
  • Overexpression of NR3C1 attenuated Quercetin's therapeutic effects on cancer cells.
  • Quercetin administration suppressed tumor growth in vivo, mirroring in vitro findings regarding apoptosis, ER stress, and ICD.
  • Bioinformatics analysis indicated NR3C1 promotes immune escape in gastric cancer.

Conclusions:

  • Quercetin exhibits potent anticancer activity against gastric cancer by targeting NR3C1.
  • Quercetin effectively reduces cancer cell viability and proliferation, while inducing ER stress, apoptosis, and ICD.
  • NR3C1 emerges as a potential therapeutic target for Quercetin-based gastric cancer treatment strategies.

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