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Preparation of Naringenin Solution for In Vivo Application
Published on: August 10, 2021
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.
Abstract:
Colorectal cancer (CRC) remains one of the most prevalent and lethal malignancies worldwide. Natural products derived from Traditional Chinese Medicine (TCM), offer promising therapeutic potential due to their multitarget effects and low toxicity. Naringenin (NAR), a major flavonoid found in citrus peel (chenpi), has shown anticancer activity in several tumor types; however, its mechanism in CRC remains incompletely understood. We combined network pharmacology, molecular docking, and experimental validation to explore the anti-CRC mechanisms of NAR. Bioinformatics databases were used to identify overlapping targets between NAR and CRC. Enrichment analyses and protein-protein interaction (PPI) networks were performed. The interaction between NAR and core targets was confirmed via molecular docking. In vitro assays (CCK-8, colony formation, flow cytometry, Transwell) and Western blotting were used to assess the functional and molecular effects of NAR and Gankyrin modulation. In vivo efficacy and toxicity were evaluated using a CRC xenograft model in nude mice. Network pharmacology identified AKT1 as a hub target, and pathway enrichment highlighted PI3K-AKT signalling. Naringenin (NAR) dose-dependently suppressed colorectal cancer (CRC) cell proliferation, migration and invasion, while promoting apoptosis. In vivo, NAR significantly inhibited tumour growth without overt systemic toxicity. Mechanistically, NAR attenuated the Gankyrin-PI3K-AKT-GSK-3β-β-catenin axis. In gain-of-function rescue experiments, Gankyrin overexpression partially blunted the anti-proliferative and anti-invasive effects of NAR, supporting a Gankyrin-dependent component of NAR activity. This study reveals that NAR exerts anti-CRC effects by targeting the Gankyrin/ PI3K/AKT/GSK-3β/β-catenin pathway, supporting its potential as a safe and effective therapeutic agent in CRC treatment.
Supplementary Information:
The online version contains supplementary material available at 10.1007/s10616-026-00948-2.
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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