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Quercetin Induces Apoptosis in HepG2 Cells via Directly Interacting with YY1 to Disrupt YY1-p53 Interaction
Hui Guan1, Wenyuan Zhang1, Hui Liu1
1Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, College of Food Science and Engineering, Shandong Agricultural University, 61 Dai Zong Street, Tai'an 271018, China.
Abstract:
Quercetin is a flavonol found in edible plants and possesses a significant anticancer activity. This study explored the mechanism by which quercetin prevented liver cancer via inducing apoptosis in HepG2 cells. Quercetin induced cell proliferation and apoptosis through inhibiting YY1 and facilitating p53 expression and subsequently increasing the Bax/Bcl-2 ratio. The results revealed that YY1 knockdown promoted apoptosis, whilst YY1 overexpression suppressed apoptosis via direct physical interaction between YY1 and p53 to regulate the p53 signaling pathway. Molecular docking using native and mutant YY1 proteins showed that quercetin could interact directly with YY1, and the binding of quercetin to YY1 significantly decreased the docking energy of YY1 with p53 protein. The interactions between quercetin and YY1 protein included direct binding and non-bonded indirect interactions, as confirmed by cellular thermal shift assay, UV-Vis absorption spectroscopy, fluorescence spectroscopy and circular dichroism spectroscopy. It was likely that quercetin directly bound to YY1 protein to compete with p53 for the binding sites of YY1 to disrupt the YY1-p53 interaction, thereby promoting p53 activation. This study provides insights into the mechanism underlying quercetin's anticancer action and supports the development of quercetin as an anticancer therapeutic agent.
Insights
Quercetin, a plant flavonol, combats liver cancer by triggering apoptosis in HepG2 cells. It inhibits the YY1 protein, enhancing p53 activity and promoting cancer cell death.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Quercetin is a naturally occurring flavonol with demonstrated anticancer properties.
- Hepatocellular carcinoma (HCC) remains a significant global health concern, necessitating novel therapeutic strategies.
- Understanding the molecular mechanisms of natural compounds like quercetin is crucial for drug development.
Purpose of the Study:
- To elucidate the mechanism by which quercetin exerts its anticancer effects on HepG2 liver cancer cells.
- To investigate the role of the Yin Yang 1 (YY1) and p53 proteins in quercetin-induced apoptosis.
- To determine if quercetin directly interacts with YY1 to modulate the p53 signaling pathway.
Main Methods:
- Cell proliferation and apoptosis assays in HepG2 cells treated with quercetin.
- Western blotting to assess p53 and Bax/Bcl-2 expression levels.
- Molecular docking simulations, cellular thermal shift assay (CETSA), UV-Vis spectroscopy, fluorescence spectroscopy, and circular dichroism (CD) spectroscopy to analyze quercetin-YY1-p53 interactions.
Main Results:
- Quercetin treatment inhibited HepG2 cell proliferation and induced apoptosis.
- Quercetin downregulated YY1 expression and upregulated p53 expression, increasing the Bax/Bcl-2 ratio.
- Molecular docking and biophysical assays confirmed direct binding of quercetin to YY1, disrupting the YY1-p53 interaction and promoting p53 activation.
Conclusions:
- Quercetin prevents liver cancer by inducing apoptosis in HepG2 cells through the inhibition of YY1 and subsequent activation of the p53 signaling pathway.
- Quercetin directly binds to YY1, competing with p53 for binding sites and disrupting their interaction.
- These findings support the potential of quercetin as a therapeutic agent for liver cancer.
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