Related Experiment Video
Updated: Jan 5, 2026
Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease
Published on: May 10, 2024
Beyond its antioxidant properties: Quercetin targets multiple signalling pathways in hepatocellular carcinoma in rats
Yasmin Ahmed Salama1, Amro El-Karef2, Amal Mohamed El Gayyar3
1Department of Biochemistry, Faculty of Pharmacy, Mansoura University, 35516, Egypt; Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, International Coastal Road, Gamasa City, 35712, Egypt.
Aims:
Hepatocellular carcinoma (HCC) pathogenesis involves the interplay of multiple signalling pathways. Notch and Hedgehog (Hh) are two major developmental pathways that act in concert to regulate adult cell repair. CK2α -serine-threonine kinase-down-regulation enhanced apoptotic activity and was proven beneficial for HCC patients. Quercetin is a bioactive flavonoid and has been shown to protect against HCC through its antioxidant activity. This study was carried out to elucidate the antineoplastic effect of quercetin through regulating both Notch and Hh pathways, apoptosis, cell proliferation and CK2α activity.
Main Methods:
Hepatocellular carcinoma was induced in male Sprague Dawley rats by thioacetamide. Quercetin was administered in both protective and curative doses. Parameters of liver function and oxidative stress were assessed. CK2α, Notch and Hh pathways were evaluated using RT-PCR and ELISA. Apoptosis was investigated by detecting caspase-3, caspase-8 and p53. Proliferative and cell cycle markers as cyclin D1 and Ki-67 were detected immunohistochemically.
Key Findings:
Quercetin inhibited CK2α and downregulated mRNA and protein expression of Notch1 and Gli2. Quercetin also suppressed caspase-3 expression but not caspase-8. Quercetin elevated p53 expression whereas proliferative and cell cycle markers cyclin D1 and Ki-67 were downregulated. Markers of hepatic cellular integrity such as AST, ALT, ALP, GGT, albumin and bilirubin were significantly ameliorated. This was confirmed by histological examination. Quercetin also alleviated oxidative stress as shown by SOD, GSH, MDA and NO levels.
Significance:
We can conclude that in addition to its antioxidant power, quercetin blocked Notch, Hedgehog, regulated the apoptotic and proliferative pathways and inhibited CK2α in HCC.
Insights
Quercetin, a flavonoid, combats hepatocellular carcinoma (HCC) by inhibiting CK2α, downregulating Notch and Hedgehog pathways, and modulating apoptosis and cell proliferation. It also reduces oxidative stress and improves liver function in rats.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Hepatocellular carcinoma (HCC) pathogenesis involves complex signaling pathways, including Notch and Hedgehog (Hh).
- Downregulation of CK2α (casein kinase 2 alpha) kinase activity is beneficial in HCC.
- Quercetin, a flavonoid with antioxidant properties, shows potential in protecting against HCC.
Purpose of the Study:
- To investigate the antineoplastic effects of quercetin in HCC.
- To elucidate quercetin's mechanism of action through modulation of Notch and Hh pathways.
- To assess quercetin's impact on apoptosis, cell proliferation, and CK2α activity in HCC.
Main Methods:
- HCC was induced in Sprague Dawley rats using thioacetamide.
- Quercetin was administered in protective and curative doses.
- Gene and protein expression (CK2α, Notch, Hh, caspases, p53, cyclin D1, Ki-67) and liver function/oxidative stress markers were analyzed.
Main Results:
- Quercetin inhibited CK2α and downregulated Notch1 and Gli2 (Hh pathway).
- Quercetin modulated apoptosis by affecting caspase-3 and p53 expression, and suppressed proliferation markers (cyclin D1, Ki-67).
- Quercetin ameliorated liver function markers and reduced oxidative stress.
Conclusions:
- Quercetin exhibits antineoplastic effects in HCC beyond its antioxidant activity.
- Quercetin effectively inhibits CK2α and modulates the Notch and Hedgehog signaling pathways.
- Quercetin regulates apoptotic and proliferative pathways, offering therapeutic potential for HCC.
