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Published on: July 12, 2018
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.
Abstract:
Gastric cancer is a major global health issue with limited treatment options. Quercetin, a natural flavonoid, has shown anticancer effects, but its mechanisms and molecular targets in gastric cancer remain unclear. This study aims to evaluate the impact of Quercetin on gastric cancer cells, focusing on its potential target, nuclear receptor subfamily 3 group C member 1 (NR3C1). AGS and MKN45 gastric cancer cells were treated with Quercetin, and cell viability, proliferation, apoptosis, endoplasmic reticulum (ER) stress, and immunogenic cell death (ICD) were assessed using standard assays. PharmMapper was utilized to predict potential targets of Quercetin in gastric cancer cells. The role of NR3C1 was further validated by introducing an NR3C1 overexpression plasmid into Quercetin-treated cells, followed by assessing changes in cellular behavior. A subcutaneous mouse tumor model was established, and the expression of NR3C1, ICD, apoptosis, and ER stress markers was detected by Western blot. Quercetin significantly reduced the viability and proliferation of gastric cancer cells while promoting apoptosis, ER stress and ICD. NR3C1 was identified as a molecular target of Quercetin. Overexpression of NR3C1 counteracted Quercetin's effects on proliferation, apoptosis, ER stress, and ICD in gastric cancer cells, highlighting its key role in mediating these outcomes. The addition of Quercetin inhibited subcutaneous tumor growth. In vivo results also indicated that Quercetin had similar effects on tumor proliferation, apoptosis, ER stress, and ICD as observed in the in vitro experiments. The bioinformatics analysis results show that NR3C1 can promote immune escape. Quercetin exhibits strong anticancer effects in gastric cancer by targeting NR3C1, reducing cell viability and proliferation while inducing ER stress, apoptosis, and ICD. These results highlight NR3C1 as a potential therapeutic target for Quercetin-based gastric cancer treatments.
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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