Quercetin induces G2 phase arrest and apoptosis with the activation of p53 in an E6 expression‑independent manner in HPV‑positive human cervical cancer‑derived cells

Clemente‑Soto, Aldo F.; Salas‐Vidal, Enrique; Milan‐Pacheco, Cesar; Sánchez‐Carranza, Jessica Nayelli; Peralta‐Zaragoza, Oscar; González‐Maya, Leticia

doi:10.3892/mmr.2019.9850

Cited by 52 publications

(43 citation statements)

References 34 publications

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“…Reciprocally, the acute/high stress promotes p53 expression and initiates DNA fragmentation to induce apoptosis via caspase cascade signaling [165]. Several flavonols are reported to cause cell cycle arrest at G2/M phase and triggered apoptosis in different types of human cancer cells via the activation of p53 [54,166,167].…”

Section: Molecular Mechanisms Underlying the Physiological Effects Ofmentioning

confidence: 99%

Allium Flavonols: Health Benefits, Molecular Targets, and Bioavailability

2020

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Allium species are revered worldwide as vegetables, condiments, and spices as well as the therapeutic agents in traditional medicine. The bioactive compounds in alliums mainly include organosulfur compounds, polyphenols, dietary fibers, and saponins. Flavonoids, particularly flavonols from alliums, have been demonstrated to have the antioxidant, anticancer, hypolipidemic, anti-diabetic, cardioprotective, neuroprotective, and antimicrobial activities. However, flavonols are mostly characterized from onions and have not been comprehensively reviewed across different species. This article therefore focuses on flavonol profiles from different Allium species, their health effects, underlying molecular mechanisms, and bioavailability. Intriguingly, the functional health effects of flavonols were mainly ascribed to their antioxidant and anti-inflammatory activities involving a cascade of multiple signaling pathways. Although the Allium-derived flavonols offer tremendous potential in preventing chronic disease risks, in-depth studies are needed to translate their clinical application.

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Section: Molecular Mechanisms Underlying the Physiological Effects Ofmentioning

confidence: 99%

Allium Flavonols: Health Benefits, Molecular Targets, and Bioavailability

2020

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“… 12 , 13 Increasing numbers of studies demonstrate that quercetin induces apoptosis of cervical cancer cells through various signal pathways. 14–16 Recently, the combination of quercetin and anticancer chemicals has been extensively studied in multiple cancer cells. Quercetin enhances the sensitivity of prostate cancer cells to paclitaxel 17 and has a synergistic effect with cisplatin on oral squamous cell carcinoma.…”

Section: Introductionmentioning

confidence: 99%

Effects of Quercetin on the Efficacy of Various Chemotherapeutic Drugs in Cervical Cancer Cells

Xu¹,

Xie²,

Chen³

et al. 2021

DDDT

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Purpose This study aimed to investigate the effects of quercetin on the efficacy of various chemotherapeutic drugs in cervical cancer cells. Methods All drug experiments were performed in HeLa and SiHa cells. The cell viability was detected by Cell Counting Kit-8 assay, and cell proliferation was estimated by bromodeoxyuridine assay. CompuSyn software was utilized to calculate the combination index (CI) and evaluate the synergistic or antagonistic effect of quercetin with cisplatin, paclitaxel, 5-fluorouracil and doxorubicin on cell viability. Cell migration and invasion abilities were detected by transwell assays, and cell apoptosis was measured by flow cytometry. The expression levels of matrix metallopeptidase 2 (MMP2), ezrin, P-glycoprotein (P-Gp) and methyltransferase-like 3 (METTL3) protein treated with various drugs were analyzed by Western blotting. Results Quercetin inhibited the viability of HeLa and SiHa cells in a dose- and time-dependent manner. The CI values of quercetin with cisplatin, paclitaxel, 5-fluorouracil and doxorubicin were <1, >1, >1 and >1, respectively. The effect of combination of quercetin and cisplatin on cell proliferation was stronger than their individual effects. Co-treatment group could inhibit more cell migration and invasion in contrast to single-drug group. Besides, quercetin combined with cisplatin group induced more cell apoptosis in contrast to single-drug group. The results of Western blotting showed that the expression levels of MMP2, ezrin, P-Gp and METTL3 in co-treatment group were lower than in cisplatin group, respectively. Conclusion Quercetin and cisplatin had synergistic inhibitory effect on cervical cancer cells. Quercetin might enhance the antitumor effect of cisplatin via inhibiting proliferation, migration and invasion and elevating apoptosis through weakening MMP2, ezrin, METTL3 and P-Gp expression of cancer cells.

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“…TP53 is one of the four major drivers of PCPL, and it can be deleted or mutate in the late stages of PCPL [51,53]. Studies have shown that quercetin can induce cell cycle arrest and p53/Bax-dependent cell apoptosis, downregulate Akt expression, and inhibit cell differentiation and proliferation [54][55][56][57][58]. β-sitosterol, another important active component of SSG, has important anti-tumour effects, facilitated through its roles in cell cycle arrest and apoptosis induction.…”

Section: Discussionmentioning

confidence: 99%

A Network Pharmacology Approach to Determine the Mechanisms of Action of Shuangshen Granules in Suppressing Pancreatic Cancer Precursor Lesions

Jiang

Zhang

Yang

et al. 2020

Preprint

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Background and purpose: Pancreatic cancer is an insidious and highly lethal disease. Recognition and treatment of pancreatic cancer precursor lesions (PCPL) are important measures and can improve patient survival rate. Shuangshen Granules (SSG) have been prescribed for use in clinical practice for more than seven years and are widely used to treat the precursor lesions of various tumours. In this study, we used network pharmacology to explore the pharmacological mechanisms through which SSG suppress PCPL. We aimed to provide a basis for further research and the development of small, molecular, natural chemical drugs.Methods: We first searched databases and screened the bioactive components of SSG and the related targets acting on PCPL to construct a component-target network. Then, network topology analysis was used to analyse the hub target of SSG acting on PCPL. Enrichment analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were also performed to determine the potential pathways. Finally, molecular docking simulations were carried out to investigate the interactions between PCPL-target proteins and the active components of SSG.Results: Seven of the main components of SSG affected PCPL, with 100 key targets including 16 hub targets. In addition, GO and KEGG enrichment analysis revealed that SSG regulated 111 molecular functions, 46 cellular components, 2334 biological processes, and 144 related signalling pathways, of which 26 were closely related to PCPL. Results of molecular docking analysis showed that the PCPL-related targets had strong binding properties with the active components of SSG, quercetin, and ginsenoside rh2, mainly TNF, IL-6, AKT1, TP53, and EGFR.Conclusion: This study has revealed the pharmacological and molecular mechanisms through which SSG acts on PCPL. It also provides powerful evidence to support the exploration of the pharmacological mechanisms of action and clinical applications of traditional Chinese medicine.

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Quercetin induces G2 phase arrest and apoptosis with the activation of p53 in an E6 expression‑independent manner in HPV‑positive human cervical cancer‑derived cells

Cited by 52 publications

References 34 publications

Allium Flavonols: Health Benefits, Molecular Targets, and Bioavailability

Allium Flavonols: Health Benefits, Molecular Targets, and Bioavailability

Effects of Quercetin on the Efficacy of Various Chemotherapeutic Drugs in Cervical Cancer Cells

A Network Pharmacology Approach to Determine the Mechanisms of Action of Shuangshen Granules in Suppressing Pancreatic Cancer Precursor Lesions

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